Determinants of Choice of Facility-Based Delivery among Mothers in Kwara State, Nigeria.

BACKGROUND: Nigeria has the highest number of maternal deaths in the world, which is a major public health problem. One of the major contributory factors is high prevalence of unskilled birth attendance from low facility delivery. However, the reasons for and against facility delivery are complex and not fully understood. OBJECTIVE: The objective of this study was to identify the facilitators and barriers to facility based deliveries (FBD) among mothers in Kwara state, Nigeria. METHODS: The study was carried out among 495 mothers that delivered in the five years prior to the study in three selected communities from the three senatorial districts of Kwara state using mixed methods. The study design consisted of a cross-sectional study with mixed data collection involving qualitative and quantitative methods. Multistage sampling technique was employed. Primary outcome measures were place of delivery, reasons for and against FBD. RESULTS: Of the 495 respondents that had their last delivery during the study period, 410 respondents delivered in the hospital (83%). Common reasons for hospital delivery were ease and convenience (87.1%), safe delivery (73.6%) and faith in healthcare providers (22.4%). The common barriers to FBD included high cost of hospital delivery (85.9%), sudden birth (58.8%) and distance (18.8%). Other important barriers were availability of cheaper alternatives (traditional birth attendants and community health extension workers practising at home), unavailability of community health insurance and lack of family support. Parity, level of education of respondents and husband had significant influence on choice of delivery (p<0.05). CONCLUSION: These findings provided a good insight into the reasons for and against facility delivery among Kwara women, which can assist policy makers and program interventions that can improve facility deliveries and ultimately improve skilled birth attendance, reduce maternal and newborn morbidity and mortality.

CONTEXTE: Le Nigeria compte le plus grand nombre de décès maternels au monde, ce qui constitue un problème majeur de santé publique. L'un des principaux facteurs contributifs est la forte prévalence de l'assistance à l'accouchement non qualifiée due à un accouchement dans des établissements de faible qualité. Cependant, les raisons pour et contre la prestation en établissement sont complexes et ne sont pas entièrement comprises. OBJECTIF: L'objectif de cette étude était d'identifier les facilitateurs et les obstacles aux accouchements en établissement (FBD) chez les mères de l'État de Kwara, au Nigeria. METHODES: L'étude a été menée auprès de 495 mères qui ont accouché au cours des cinq dernières années précédant l'étude dans trois communautés sélectionnées des trois districts sénatoriaux de l'État de Kwara en utilisant des méthodes mixtes. La conception de l'étude consistait en un entretien avec des informateurs clés et une étude transversale avec une collecte de données mixte impliquant des méthodes qualitatives et quantitatives. La technique d'échantillonnage à plusieurs degrés a été employée. Les principaux critères de jugement étaient le lieu d'accouchement, les raisons pour et contre le FBD. RESULTATS: Parmi les 495 répondantes qui ont eu leur dernier accouchement au cours de la période d'étude, 410 répondantes ont accouché à l'hôpital (83 %). Les raisons courantes de l'accouchement à l'hôpital étaient la facilité et la commodité (87,1 %), la sécurité de l'accouchement (73,6 %) et la confiance dans les prestataires de soins de santé (22,4 %). Les obstacles courants à la FBD comprenaient le coût élevé de l'accouchement à l'hôpital (85,9 %), l'accouchement soudain (58,8 %) et la distance (18,8 %). D'autres obstacles importants étaient la disponibilité d'alternatives moins chères (accoucheuses traditionnelles et agents de vulgarisation de la santé communautaire exerçant à domicile), l'absence d'assurance maladie communautaire et le manque de soutien familial. La parité, le niveau d'éducation des répondants et le mari ont une influence significative sur le choix de l'accouchement (p<0,05). CONCLUSION: Ces résultats ont fourni un bon aperçu des raisons pour et contre l'accouchement en établissement chez les femmes Kwara, ce qui peut aider les décideurs politiques et les interventions de programme qui peuvent améliorer les accouchements en établissement et, en fin de compte, améliorer l'assistance qualifiée à l'accouchement, réduire la morbidité et la mortalité maternelles et néonatales. Mots clés: Prestation en établissement; Facilitateurs; Barrières; État de Kwara; Nigeria.

Beneficial impact of Nesfatin-1 on reproductive dysfunction induced by nicotine in male rats: Possible modulation of autophagy and pyroptosis signaling pathways.

This study was conducted to explore the beneficial impact of nesfatin-1 on reproductive dysfunction induced by nicotine (NT) in male rats with possible modulation of autophagy and pyroptosis signaling pathways. This research was performed on 40 Wistar male rats. They were distributed into four groups: control, normal+nesfatin-1, NT, and NT+nesfatin-1. At the end of the experimental period, the serum was separated for assay of testosterone, FSH and LH. Also, sperm parameters were determined. Histopathological examination of testicular tissue and immunohistochemical analysis was done for mammalian target of rapamycin, AMP-activated protein kinase, and mitogen-activated protein kinases including phosphorylated extracellular signal regulated kinase and phosphorylated cJun N-terminal kinase. Relative gene expression was determined for testicular nucleotide oligomerization domain (NOD)-like receptors proteins and Caspase-1, and autophagy markers including microtubule-associated protein 1 light chain 3 alpha and Beclin-1. Also, the following testicular parameters were assayed: 3ß-hydroxysteroid dehydrogenase, 17ß-hydroxysteroid dehydrogenase, malondialdehyde, superoxide dismutase activity, catalase, glucose-6 phosphate dehydrogenase, reactive oxygen species, caspase-3 activity, IL-1ß, IL-18, mitochondrial transmembrane potential and Complex-I activity. The results revealed that the normal+nesfatin-1 group showed insignificant changes as compared to the control group. Meanwhile, the NT group exhibited prominent reproductive dysfunction in male rats. On the other hand, in the NT+nesfatin-1 group nesfatin-1 notably attenuated this reproductive dysfunction as evidenced by improvement of hormonal assay, sperm parameters, histopathological picture, immunohistochemical evaluation and real time relative gene expressions. In conclusion: Nesfatin-1 alleviated the impairment of male reproductive functions induced by NT via enhancement of autophagy pathways, suppression of pyroptosis, apoptosis, mitochondrial dysfunction and ROS production. Thus nesfatin-1 may offer a novel protective or therapeutic access for treating male infertility.

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

The possible role of heat shock protein-70 induction in collagen-induced arthritis in rats.

AIM: This study aimed to evaluate the possible role of heat shock protein-70 (HSP70) induction by 17-allylaminodemethoxygeldanamycin (17-AAG) in collagen-induced arthritis in rats. MATERIAL AND METHODS: Male Wistar rats were divided into five groups (n = 10/group) and were treated intraperitoneally twice a week for 4 weeks, namely normal control (saline), arthritis control (AR; saline), AR + 17-AAG, AR + methotrexate (MTX), and AR + 17-AAG + MTX. At the end of the treatments, arthritic score was determined and then the animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx), and matrix metalloproteinase-9 (MMP-9) were determined. RESULTS: In the AR group, all parameters increased significantly, except for GPx, which showed a pronounced decrease. The 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-α, RF, CRP, MDA, and MMP-9 with significant increase in GPx compared to the AR group. The HSP70 level was significantly higher in the AR + 17-AAG and the AR + 17-AAG + MTX groups but significantly lower in the AR + MTX group as compared to the AR group. Also, it was significantly lower in the AR + MTX group as compared to the AR + 17-AAG group. CONCLUSION: We concluded that HSP70 induction by 17-AAG attenuated the inflammatory process in a rheumatoid arthritis (RA) model induced by collagen, which suggested that HSP70 inducers can be promising agents in the treatment of RA.

Long-term outcome after proximal gastrectomy with jejunal interposition for suspected early cancer in the upper third of the stomach.

BACKGROUND: Proximal gastrectomy was introduced as a function-preserving operation for early gastric cancer (EGC). The aim of this study was to investigate long-term outcomes after this procedure. METHODS: Between 1993 and 2005, patients with suspected EGC in the upper third of the stomach underwent proximal gastrectomy. The long-term oncological and surgical outcomes were assessed. RESULTS: Of 128 patients thought to have EGC, 14 had advanced disease. Nodal involvement was seen in 13 patients (10.2 per cent). Postoperative complications developed in 20 (15.6 per cent). Anastomotic stricture was the most frequent complication, occurring in 13 patients (10.2 per cent). There were no postoperative deaths. During follow-up, nine patients (7.0 per cent) were hospitalized owing to bowel obstruction. Eight (6.3 per cent) developed a second primary gastric carcinoma. The overall 5-year survival rate was 90.5 per cent. CONCLUSION: Proximal gastrectomy is well tolerated, with excellent outcomes in patients with suspected EGC. It is recommended as a standard procedure for the treatment of EGC in the upper third of the stomach.

Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo.

BACKGROUND AND PURPOSE: Proteinase-activated receptor 2 (PAR(2)) is a G-protein coupled receptor associated with many pathophysiological functions. To date, the development of PAR(2) antagonists has been limited. Here, we identify a number of novel peptide-mimetic PAR(2) antagonists and demonstrate inhibitory effects on PAR(2)-mediated intracellular signalling pathways and vascular responses. EXPERIMENTAL APPROACH: The peptide-mimetic compound library based on the structures of PAR(2) agonist peptides were screened for inhibition of PAR(2)-induced calcium mobilisation in human keratinocytes. Representative compounds were further evaluated by radioligand binding and inhibition of NFkappaB transcriptional activity and IL-8 production. The vascular effects of the antagonists were assessed using in vitro and in vivo models. KEY RESULTS: Two compounds, K-12940 and K-14585, significantly reduced SLIGKV-induced Ca(2+) mobilisation in primary human keratinocytes. Both K-12940 and K-14585 exhibited competitive inhibition for the binding of a high-affinity radiolabelled PAR(2)-ligand, [(3)H]-2-furoyl-LIGRL-NH(2), to human PAR(2) with K(i) values of 1.94 and 0.627 microM respectively. NFkappaB reporter activity and IL-8 production were also significantly reduced. Furthermore, relaxation of rat-isolated aorta induced by SLIGRL-NH(2) was inhibited competitively by K-14585. K-14585 also significantly lowered plasma extravasation in the dorsal skin of guinea pigs and reduced salivation in mice. CONCLUSIONS AND IMPLICATIONS: K-12940 and K-14585 antagonized PAR(2) competitively, resulting in inhibition of PAR(2)-mediated signalling and physiological responses both in vitro and in vivo. These peptide-mimetic PAR(2) antagonists could be useful in evaluating PAR(2)-mediated biological events and might lead to a new generation of therapeutically useful antagonists.

The prognostic impact of isolated tumor cells in lymph nodes of T2N0 gastric cancer: comparison of American and Japanese gastric cancer patients.

BACKGROUND: The clinical significance of immunohistochemically detected isolated tumor cells (ITC) in lymph nodes of gastric cancer patients is controversial. This study examined the prognostic impact of ITC on patients with early-stage gastric cancer in two large volume centers in the United States and Japan. METHODS: Fifty-seven patients with T2N0M0 gastric carcinoma who underwent gastric resection between January 1987 and January 1997 at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and 107 patients resected at National Cancer Center Hospital (NCCH) in Tokyo between January 1984 and December 1990 were studied. The sections were newly prepared from each lymph node for immunohistochemical staining for cytokeratin. Lymph nodes and original specimens from MSKCC were examined by pathologists in NCCH. The prognostic significance of the presence of ITC in lymph nodes was investigated in patients of both institutions. RESULTS: ITC were identified in 30 of 57 patients (52.6%) at MSKCC and in 38 of 107 patients (35.5%) at NCCH. In both institutions, there was no significant difference in the prognosis of the studied patients with or without ITC (P= .22, .86 respectively). CONCLUSIONS: The presence of ITC detected by immunohistochemistry in the regional lymph nodes did not affect the prognosis of American and Japanese patients with T2N0M0 gastric carcinoma who underwent gastrectomy with D2 lymph node dissection.

Persistent dystonia induced by fluoxetine.

Serotonin-selective re-uptake inhibitors are prescribed widely because they are regarded as having less severe side-effects compared with tricyclics and monoamine oxidase inhibitors. With this popularity, increasing attention has been drawn to their adverse effects. Development of extrapyramidal symptoms has been reported in some patients while taking fluoxetine, a commonly used serotonin-selective re-uptake inhibitor. Here, we report a case of persistent dystonia, thought to be associated with short-term fluoxetine use, which required treatment with botulinum toxin type A.

Outcome of pylorus-preserving gastrectomy for early gastric cancer.

BACKGROUND: Pylorus-preserving gastrectomy has been introduced as a function-preserving operation for early gastric cancer in Japan. The aim of this study was to investigate the safety and radicality of the procedure. METHODS: Between 1995 and 2004, 611 patients with apparent early gastric cancer in the middle third of the stomach had pylorus-preserving gastrectomy. The short-term surgical and long-term oncological outcomes of these operations were assessed. RESULTS: The accuracy of preoperative diagnosis of early gastric cancer was 94.3 per cent. Nodal involvement was seen in 62 patients (10.1 per cent). There were no postoperative deaths. Complications developed in 102 patients (16.7 per cent). Major complications, such as leakage and abscess, were observed in 19 (3.1 per cent). The most common complication was gastric stasis, occurring in 49 (8.0 per cent). The overall 5-year survival rate in patients with early gastric cancer was 96.3 per cent. CONCLUSION: Pylorus-preserving gastrectomy is a safe operation with an excellent prognosis in patients with early gastric cancer. It is recommended as the standard procedure for early gastric cancer in the middle third of the stomach.

[The factor structure of schizophrenic symptoms: which model is supported by independent item analysis?]. / Sizofreni belirtilerinin faktör yapisi: bagimsiz madde analizi nasil bir modeli destekliyor?

OBJECTIVE: Most studies that have investigated the symptom dimensions of schizophrenia utilizing the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS), both global rating scales, favored a 3-factor model. Only a few studies have examined the factor structure at the item level and they suggest a wider dimensional structure. The factor structure of schizophrenic symptoms has not been previously studied in Turkey, nor has the construct validity of these scales. The present study sought to determine the factor structure of the independent items and the construct validity of the scales. METHOD: The study included 180 schizophrenia patients (diagnoses based on DSM-IV criteria). The standard statistical methods of principal component analysis (PCA) and varimax rotation were used to extract factors. RESULTS: PCA of the global items yielded a 3-factor solution, representing positive, negative, and disorganization dimensions. Item-level factor analysis revealed 12 factors: Psychomotor poverty, positive formal thought disorder, auditory/visual hallucinations, social and occupational dysfunction, bizarre delusions, attention/stereotypy, paranoid features, somatic hallucinations/delusions, appearance, grandiose/religious delusions, inappropriate affect, and delusions of jealousy. CONCLUSION: Consistent with previous studies, neither the global nor the item-level factor structures supported the simple positive-negative dichotomy or the composition of the sub-scales; therefore, future studies should make use of the single items, especially when positive symptoms are being studied.

Distribution and significance of the oesophageal and gastric cardiac mucosae: a study of 131 operation specimens.

AIMS: To clarify the distribution and significance of the oesophageal and gastric cardiac mucosae at the oesophago-gastric junction (EGJ). METHODS AND RESULTS: Oesophagectomy specimens from 131 consecutive patients with middle and upper thoracic oesophageal cancer were examined. The surgically resected specimens including the EGJ were cut into 5 mm thick serial sections and examined histopathologically for the length of the oesophageal and gastric cardiac mucosae and the incidence of columnar epithelial islands (CEIs). We also determined the presence of short-segment Barrett's oesophagus (SSBE) and goblet cell metaplasia in SSBE. Oesophageal cardiac mucosa was found in 125 cases (95%) and gastric cardiac mucosa was found in all cases. The mean length of the oesophageal and gastric cardiac mucosa was 4 mm (range 1-26 mm) and 13 mm (range 2-64 mm), respectively. CEIs were found in 75 cases (57%). SSBE was found in 70 cases (53%), among which goblet cell metaplasia was found in 28 cases (21%). No long-segment Barrett's oesophagus was found. The mean length of oesophageal cardiac mucosa (6 mm) and gastric cardiac mucosa (17 mm) in SSBE was significantly greater than that (3 mm and 8 mm, respectively) in non-SSBE cases (P < 0.0001 and P < 0.0001). The incidence (69%) of CEIs in SSBE was significantly higher than that (44%) in non-SSBE cases (P = 0.005). CONCLUSIONS: Oesophageal and gastric cardiac mucosae were found frequently. Oesophageal cardiac glands and CEIs might play an important role in the development of SSBE.

Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren's syndrome model mice.

Regulation of the adhesion of mononuclear cells to endothelial cells is considered to be a critical step for the treatment of inflammatory diseases, including autoimmune diseases. K-13182 was identified as a novel inhibitor for these adhesions. K-13182 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) on human umbilical vein endothelial cells (HUVECs) and on mouse vascular endothelial cell line (MAECs) induced by tumour necrosis factor (TNF)-alpha. K-13182 also inhibited the adhesion of mononuclear cells to these HUVECs and MAECs, indicating that K-13182 suppressed these adhesions mediated by cellular adhesion molecules including VCAM-1. To evaluate the therapeutic effect in autoimmune disease model mice, K-13182 was orally administered to non-obese diabetic (NOD) mice as Sjögren's syndrome (SS) model mice. Severe destructive inflammatory lesions were observed in the lacrimal glands of vehicle-treated control mice; however, 8-week administration of K-13182 inhibited the mononuclear cell infiltration into the inflammatory lesions of the lacrimal glands. In K-13182-treated mice, the decrease in tear secretion was also prevented compared to the control mice. In addition, the apoptosis and the expression of FasL (CD178), perforin, and granzyme A was suppressed in the lacrimal glands of K-13182-treated mice. Therefore, K-13182 demonstrated the possibility of therapeutic efficacy for the inflammatory region of autoimmune disease model mice. These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS.

Surgical treatment of advanced gastric cancer: Japanese perspective.

The results of clinical trials regarding surgery of curable advanced gastric cancer and esophagogastric junction (EGJ) tumors are reviewed and summarized. Four clinical trials have evaluated D2 dissection for curable gastric cancer in the West. Two large trials in the UK and the Netherlands failed to prove the efficacy of D2 dissection. However, these trials had critical weak points. As they were carried out in a number of hospitals where there was no experience with this surgery, the quality of surgery and postoperative care were very poor making the hospital mortality unacceptably high. After these trials, an Italian group started a phase II study in 8 hospitals with a relatively high volume to confirm the safety of this procedure for Caucasians. They achieved 3% mortality, which was much smaller than that of even D1 in the former trials. These results first highlighted the importance of learning and hospital volume in D2 dissection. Survival results of the Dutch trial showed some difference between D1 and D2, but the difference was not statistically significant. This was attributed to the high hospital mortality and poor quality of surgery, especially low compliance of D2 and the high rate of extension of D1, making this comparison similar to that between D1.3 and D1.7. The results of the phase III study by the Italian group are awaited. Recently a Taiwanese trial proved the benefit of D2 dissection over D1 in a phase III trial. This was a single institutional trial with a sample size of 221 patients. The 5-year survival rate of D2 and D1 was 59.5 and 53.6%, respectively (p = 0.04). The Dutch trials for EGJ tumors showed a large difference in overall survival between the transthoracic and transhiatal approach for Siewert type 1 and 2 tumors, but this was not statistically significant, most likely due to the small sample size. In the subgroup analysis, they demonstrated that there was no survival difference in Siewert type 2 but a large difference in Siewert type 1. A Japanese study showed that there is no benefit to the thoraco-abdominal approach over the transhiatal approach for EGJ tumors whose invasion in the esophagus is 3 cm or less. These two trials clearly demonstrated that mediastinal dissection through a right thoracotomy is recommendable for Siewert type 1, while the transhiatal approach should be considered as standard for Siewert type 2.

Cytokine upregulation of proteinase-activated-receptors 2 and 4 expression mediated by p38 MAP kinase and inhibitory kappa B kinase beta in human endothelial cells.

BACKGROUND AND PURPOSE: Up-regulation of proteinase-activated receptor-2 (PAR2) is a factor in a number of disease states and we have therefore examined the signalling pathways involved in the expression of the receptor. EXPERIMENTAL APPROACH: We investigated the effects of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), trypsin and the PAR2 activating peptide, 2-furoyl(2f)-LIGKV-OH on both mRNA and functional expression of PAR2 in human umbilical vein endothelial cells (HUVECs). The effect of specific chemical inhibitors and dominant negative adenovirus constructs of the mitogen-activated protein kinase (MAPK) cascade and the nuclear factor kappa B (NF-kappaB) signalling pathway was assessed. Methods included semi-quantitative and quantitative RT-PCR, [(3)H]inositol phosphate (IP) accumulation and Ca(2+)-dependent fluorescence. KEY RESULTS: The above agonists induced both mRNA and functional expression of PAR2; PAR4 mRNA, but not that for PAR1 or PAR-3, also increased following TNFalpha treatment. Inhibition of p38 MAP kinase reduced PAR2 and PAR4 expression, whilst inhibition of MEK1/ERK/JNK was without effect. A similar dependency upon p38 MAP kinase was observed for the expression of PAR4. TNFalpha -induced enhancement of PAR2 stimulated [(3)H]-inositol phosphate accumulation (IP) and Ca(2+) signalling was abolished following SB203580 pre-treatment. Infection with adenovirus encoding dominant-negative IKKbeta (Ad.IKKbeta(+/-)) and to a lesser extent dominant-negative IKKalpha (Ad.IKKalpha(+/-)), substantially reduced both control and IL-1beta- induced expression of both PAR2 and PAR4 mRNA and enhancement of PAR2-stimulated IP accumulation and Ca(2+) mobilisation. CONCLUSIONS AND IMPLICATIONS: These data reveal for the first time the signalling events involved in the upregulation of both PAR2 and PAR4 during pro-inflammatory challenge.

Production of monoclonal antibodies against Chinemys reevesii turtle vitellogenin and their usage for comparison of biochemical and immunological characters of vitellogenins and yolk proteins of freshwater turtles.

Four hybridoma clones (ACV-1, -3, -4, and -5) were established for Chinemys reevesii (Reeves' turtle) vitellogenin (VTG) as a precursor protein of egg yolk and a biomarker of environmental pollution. Binding-inhibition experiments indicated that the epitopes of four mAbs were distinct. No binding of ACV-4 to C. reevesii VTG in the Western blot suggests that the epitope of ACV-4 would be dependent on the three-dimensional structure. ACV-1, -3, and -5 bound to C. reevesii VTG in the Western blot. The signal for ACV-1 and -5 disappeared by reduction of the VTG, suggesting that the construction of the epitopes for ACV-1 and -5 were dependent on the disulfide bridge in the VTG molecule. All four mAbs recognized Trachemys scripta and Mauremys japonica VTGs in the ELISA. The yolk proteins were tested for the binding of the mAbs in the Western blot. ACV-1 being capable to bind to the VTG in the reduced condition did not bind to any protein bands of the yolk. This indicates that ACV-1 recognizes a part of the VTG molecule that is not incorporated in the oocytes. Both ACV-3 and -5 bound to the 32- and 70-kDa yolk proteins. Since a mAb recognizes only one site (epitope) on a protein molecule, the 32-kDa protein originated from the 70-kDa one. An ELISA system using ACV-5 as the capture antibody and ACV-3 as the detecting antibody showed the lower detectable concentration (2 ng/mL) and a wide detectable range to 1000 ng/mL (R2=0.999). The system was used to determine serum VTG levels of juvenile turtles treated with estradiol-17beta or vehicle (corn oil). By the use of the mAbs described in this paper, basic and applied studies for turtle VTGs would be improved.

Comparative analyses of serum vitellogenin levels in male and female Reeves' pond turtles (Chinemys reevesii) by an immunological assay.

A quantitative immunological method was developed for measuring serum vitellogenin levels of Reeves' pond turtles (Chinemys reevesii) to investigate the effects of endocrine disruptors on the freshwater ecosystem. Vitellogenin was induced by injecting estradiol-17beta into C. reevesii turtles (adult females, juvenile females, and males) and was purified from the turtle serum by EDTA-MgCl2 precipitation followed by gel filtration. Using a polyclonal antibody raised against C. reevesii vitellogenin, an enzyme-linked immunosorbant assay was established. The detectable range, recovery of vitellogenin, and coefficient of variation in this assay were 0.0040-1.0 microg.ml(-1), 85.3-109% and 3.4-11.5%, respectively. This assay was also applicable for measurement of the concentrations of vitellogenins from other species, Japanese pond turtles (Mauremys japonica) and red-eared turtles (Trachemys scripta). The serum vitellogenin concentration of 131 C. reevesii turtles captured at a Japanese local river was measured by the assay. In females, vitellogenin ranged from 0.10 microg.ml(-1) to 15,000 microg.ml(-1) with two peaks, 0.10-1.0 microg.ml(-1) (juveniles) and 1,000-10,000 microg.ml(-1) (adults). However, in males, it ranged from 0.10 microg.ml(-1) to 0.60 microg.ml(-1), showing one peak, 0.10-0.20 microg.ml(-1). Therefore, if relatively high concentrations of vitellogenin are detected in males or juvenile females, it is suggested that they would have been exposed to xenobiotic estrogens.

[Induction of mucosal immunity to mycobacterial heat shock protein (hsp) 65 by colonic inoculation of plasmid DNA encoding hsp65].

Mycobacterial heat shock protein (hsp) 65 has more than 50% sequence homology with human hsp60 and immune responses against mycobacterial hsp65 may cross-react with human hsp60 and could cause autoimmune diseases including inflammatory bowel diseases (IBD). Since the colonic mucosa is a main inflammatory site in IBD, mucosal immunity to hsp65 may be more important for the mucosal inflammation than systemic immunity to hsp65. We inoculated plasmid DNA (pDNA) encoding mycobacterial hsp65 (pACB-hsp 65) into the colon of Wistar rats and evaluated the mucosal humoral immune response and the effect of these immune responses on the colonic mucosa. Four weeks after pDNA inoculation, significantly elevated titers of hsp65-specific IgA antibody were seen in fecal extracts of rats immunized intra-colonic mucosa with pACB-hsp65 (40 +/- 9 U/ml), whereas the fecal IgA antibody titers of rats inoculated intradermal with pACB-hsp65 did not arise (8 +/- 5 U/ml). Colonic inoculation of pACB-hsp65 induced systemic and mucosal immune responses to hsp65. However, macroscopic and histological examinations of the colonic mucosa inoculated with pACB-hsp65 showed no evidence of mucosal damage. These results suggested that the mucosal immunity to hsp65 on the colonic mucosa may not play a crucial role in the induction of colonic mucosal inflammation as was seen in IBD.

Protein-losing enteropathy exacerbated with the appearance of symptoms of systemic lupus erythematosus.

A 38-year-old woman visited our hospital with edema on her face and conjunctivae. The underlying disease was not clarified, and she did not visit the hospital afterwards. She suffered from diarrhea, polyarthralgia, Raynaud's phenomenon, malar rash and hair loss in the subsequent two years, and was hospitalized because of hypoproteinemia. Her urine, liver and heart test results did not account for her hypoproteinemia. She was diagnosed as having protein-losing enteropathy (PLE) associated with SLE based on the 99mtechnetium-labeled human serum albumin scintigraphy findings, clinical findings and laboratory results of antinuclear and anti-Sm antibodies. This case report demonstrates a strong association between PLE and SLE because PLE was aggravated along with the appearance of SLE symptoms and PLE subsided with prednisolone treatment along with improvement of SLE.

[Current status and problem of adjuvant chemotherapy for curatively resected gastric cancer].

Randomized controlled trials (RCT) on adjuvant chemotherapy for gastric cancer published in the West and Japan were reviewed. Although several small trials showed positive data, adjuvant chemotherapy for curatively resected gastric cancer has been thought to be ineffective in western countries. Results of Japanese RCTs also have not become evidence of its benefit. Despite this, suggestive data by non-predefined subset analyses of old RCTs have been misread as definitive evidence of benefit because of less understanding of clinical statistics in Japan. As a result most Japanese patients have received postoperative adjuvant chemoimmunotherapy. Recently understanding of clinical trial has spread gradually and well designed RCTs with sufficient sample size have been reported. First of all we have to determine the efficacy of adjuvant chemotherapy by carefully designed RCT using surgery alone arm as control.