An individualized mental health education programme for Japanese managers.

BACKGROUND: Mental health education for managers has typically been conducted using a group format. Few studies have examined the provision of individualized education. AIMS: This study discussed the evaluations and characteristic needs of participants in an individualized mental health education programme while examining avenues for providing such education. METHODS: Eighty-nine individualized education sessions were conducted for managers (87 males, 2 females) with a mean age of 42.6 years (SD = 5.1) at an assembly factory in Japan. Data from anonymous self-administered questionnaires completed before and after the education programme were analysed. RESULTS: Overall, 95% of the managers (81/85) approved the individualized education format. The characteristic needs of participants with high motivation (45%, 38/85) were mental health consultations for managers (37%, 14/38, 95% confidence interval [CI] 1.62-14.7, P < 0.01) and subordinate-related concerns (18%, 7/38, 95% CI 1.11-22.8, P < 0.05). CONCLUSIONS: Individualized education may be a suitable method for conducting mental health consultations. It is recommended that the introduction of individualized education formats be implemented through voluntary consultations following group education. Individualized education may contribute to early intervention for work-related mental disorders.

Lymphoepithelioma-like carcinoma of the uterine cervix: a case report.

Lymphoepithelioma-like carcinoma (LELC) is a rare variant of carcinoma of the uterine cervix, of which Epstein-Barr virus (EBV) and/or human papilloma virus (HPV) may play an important role in the pathogenesis. The authors report a case of a patient with cervical LELC who was also examined for the presence of EBV and HPV. A 31-year-old Japanese female presented with irregular genital bleeding. The biopsy showed an invasive squamous cell carcinoma. Based on the clinical data, the patient was diagnosed as having squamous cervical carcinoma, and radical hysterectomy with ovarian conservation was performed. A diagnosis of cervical LELC was then made by histological methods. An additional examination revealed that the patient was infected with HPV types 16 and 71, but not infected with EBV.

Clinical characteristics classified by the serum KL-6 level in patients with organizing pneumonia.

BACKGROUND: The serum Krebs von der Lungen-6 (KL-6) level is a useful marker correlated with the severity of various interstitial lung diseases. There have been few reports about the clinical characteristics of organizing pneumonia (OP) associated with the serum KL-6 levels. OBJECTIVE: This study was performed to determine whether the serum KL-6 levels can help determine the optimal treatment for OP. DESIGNS: Patients diagnosed with OP by clinical, radiological and histopathological findings were retrospectively reviewed. The OP patients were classified into two groups based on their serum KL-6 levels: normal KL-6 and high KL-6 groups. The two groups were compared with regard to their clinical and radiological data and therapeutic response one month after the start of treatment. RESULTS: The clinical records of twenty-two patients diagnosed with OP were reviewed. The serum KL-6 level was elevated in 11 of the 22 patients. There were no obvious differences in the clinical data between the two groups, although patients in the normal KL-6 group tended to have a fever. There were no significant differences in the chest X-ray (CXR) score or computed tomography (CT) score between the two groups. The CXR scores were correlated with the serum KL-6 levels. At 1 month after the diagnosis, 11 patients who needed treatment with prednisolone were included in the high KL-6 group. CONCLUSIONS: Patients with normal KL-6 levels showed lower CXR and CT scores. The serum KL-6 level on admission is a useful marker to judge the need for corticosteroid treatment in OP patients.

Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.

WHAT IS KNOWN AND OBJECTIVE: It has been reported that ibuprofen interferes with the antiplatelet effect of low-dose aspirin. This interaction is ascribed to steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when aspirin is administered after ibuprofen. However, whether other non-steroidal anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well defined. The aim of this study was to assess the influence of nine NSAIDs on the antiplatelet effect of aspirin. METHODS: We investigated the antiplatelet effect of NSAIDs using steady-state plasma concentration reported after usual doses. We studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin before NSAID addition and aspirin after NSAID addition to platelet-rich plasma. The rates of platelet aggregation induced by collagen were determined. The final concentration of aspirin used was the 50% effective concentration (EC(50)) previously estimated in vitro. RESULTS AND DISCUSSION: Ibuprofen and mefenamic acid interfere with the antiplatelet effect of aspirin when added before the latter. The rate of platelet aggregation was reduced by 48·1% and 22·7%, respectively. The other NSAIDs tested did not significantly affect the aspirin antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs altered the aspirin effect if administration followed that of aspirin. WHAT IS NEW AND CONCLUSION: Naproxen and flurbiprofen have significant antiplatelet effects at plasma concentrations seen with usual doses. Our in vitro model suggests that the antiplatelet effect of aspirin is significantly diminished when taken after, but not before, ibuprofen or mefenamic acid. None of the other NSAIDs tested had any effect irrespective of the timing of dosing.

LIM-homeodomain transcription factor, Lhx2, is involved in transcriptional control of brain-specific promoter/exon 1f of the mouse aromatase gene.

Neurosteroidal oestrogen has been proposed to play important roles in a variety of reproductive behaviours. Aromatase, a key enzyme in oestrogen synthesis, is localised in neural nuclei of specific brain regions and is developmentally regulated, with a transient expression peak at the perinatal period. The brain-specific promoter of the aromatase gene was analysed aiming to determine the transcriptional control mechanisms that could help explain the spatiotemporal expression. We previously reported that a 202-bp sequence, which is upstream from the transcriptional initiation site, is essential for the basal transcriptional activity. The 202-bp upstream region of brain-specific exon 1 comprises at least three types of cis-acting elements: aro-AI (Arom-Aα), aro-AII (Arom-Aß) and aro-B (Arom-B). To identify the binding proteins for the cis-acting elements, a yeast one-hybrid screen was performed with these cis-element sequences using a mouse foetal cDNA library. Lhx2, a LIM-homeodomain protein, was identified as one of the aro-B binding proteins. The identification was further confirmed using the gel shift assay, which demonstrated binding competition of nuclear proteins to the aro-B element with a typical Lhx2-binding element. In addition, a chromatin immunoprecipitation assay with an anti-Lhx2 antibody demonstrated that Lhx2 bound to the aro-B site in vivo. A reporter assay of the brain-specific promoter demonstrated increased Lhx2-dependent promoter activity. Furthermore, the time-dependent increase in aromatase mRNA in primary cultured foetal neurones was suppressed by an small-interfering RNA-mediated knockdown of Lhx2 expression. These results show that Lhx2 is involved in the transcriptional regulation of aromatase in the rodent brain.

Malignant mixed Müllerian tumor of the fallopian tube: a case report.

Malignant mixed Müllerian tumor (MMMT) of the female genital tract is uncommon and extremely rare in the Fallopian tube. We describe a case of primary MMMT of the Fallopian tube with carcinomatous and heterologous mesenchymal components in a 60-year-old woman. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, pelvic and paraaortic lymph node dissection, and resection of intrapelvic metastases. The tumor formed a large polypoid mass within the right Fallopian tube and had penetrated the wall to the paraovarian space. Microscopic examination revealed two components of poorly differentiated adenocarcinoma and high-grade sarcoma with chondromatous differentiation. The patient received six courses of adjuvant chemotherapy with ifomide and cisplatin and is currently in remission. Although MMMT in the Fallopian tube shows poor prognosis, primary cytoreductive surgery with platinum-based combination chemotherapy may improve survival.

Plasma glucose, mannose, and non-esterified fatty acid concentrations in layer-type chickens.

1. The oral administration of glucose or dietary glucose reduces fasting plasma mannose concentrations in mammals. On the other hand, there have been no reports on plasma mannose levels in birds. We have analysed chicken plasma mannose and glucose by an original high-performance liquid chromatography (HPLC) method, together with plasma non-esterified fatty acid (NEFA) concentrations in chickens. 2. Plasma glucose concentrations of chickens did not differ among three different age groups (0, 18 and 150 d). However, the plasma mannose concentrations of chicks at the age of 0 d were higher than those of chickens at the ages of 18 and 150 d. 3. At the age of 18 and 150 d, plasma glucose concentrations were elevated and plasma mannose and NEFA concentrations were decreased after regular feeding, compared to fasting levels.

Repeated paracentesis in a fetus with meconium peritonitis with massive ascites: a case report.

Meconium peritonitis (MP) is defined as a sterile inflammatory reaction in the fetal abdomen that is seen in cases of intrauterine bowel perforation. Recently, there have been increasing numbers of fetuses with MP prenatally diagnosed by ultrasonography. Massive fetal ascites in MP may cause hydrops and hypoplastic lungs. However, antepartum management of MP has not yet been established. We encountered a fetus with MP and massive ascites. Repeated paracentesis between 29 weeks and 4 days and 31 weeks and 6 days of gestation prevented the progression to fetal hydrops and hypoplastic lungs, which may occur due to massive meconium ascites with an increased preload index. Amniocentesis was also performed in patients with polyhydramnios for treatment of preterm labor. These observations suggest that aggressive therapy can prolong the gestation period and improve MP treatment outcomes.

Plasminogen activator inhibitor-1 aids nerve growth factor-induced differentiation and survival of pheochromocytoma cells by activating both the extracellular signal-regulated kinase and c-Jun pathways.

Astrocytes are thought to be critical to neurons' surviving damage caused by ischemic stroke or other injury. Plasminogen activator inhibitor-1 is one of the active soluble factors released by astrocytes and regulates plasminogen activator-plasmin proteolytic sequence in the CNS as a serpin. In this study, we show that plasminogen activator inhibitor-1 can promote neurite outgrowth and survival of rat pheochromocytoma cells in serum-deprived conditions, and that this neuroprotective activity is correlated with enhanced activation of both extracellular signal-regulated kinases following a direct phosphorylation of nerve growth factor receptor, Trk A, and of c-Jun. Our results suggest that plasminogen activator inhibitor-1 can act as a neurotrophic factor, protecting neurons from serum deprivation-induced neuron death not only by compensating for nerve growth factor functions, but also by activating the c-Jun/activating protein-1 pathway.

Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds.

In order to clarify the onset mechanisms of drug-induced allergies, three fluorescent-labelled compounds were synthesized by subjecting sulfanilamide (SA), a base compound for sulfonamides, and its active metabolites, i.e. sulfanilamide hydroxylamine and sulfanilamide nitroso, to dansylation using dansylchloride. In other words, 5-dimethylamino-N-(4-aminobenzyl)-naphthalenesulfonamide (DNS-4ABA), 5-dimethylamino-N-(4-hydroxylaminobenzyl)-1-naphthalenesulfonamide (DNS-4HABA) and 5-dimethylamino-N-(4-nitrosobenzyl)-1-naphthalenesulfonamide (DNS-4NSBA) were synthesized as model haptens. When analysed by HPLC, a conjugate of DNS-4HABA and glutathione (GSH) with nucleophilic amino acids had two peaks (P-1 and P-2). FAB-MS and 1H-NMR revealed that the DNS-4HABA-GSH conjugate consisted of sulphinamide and semimercaptal. The reactivity of GSH to DNS-4ABA, DNS-4HABA and DNS-4NSBA was quantified by HPLC using an oxidization system (horseradish peroxidase/H2O2). The results show that production of DNS-4NSBA-GSH-conjugate was four to eight times higher than that of DNS-4HABA-GSH conjugate, but that DNS-4ABA did not bind with GSH. Skin reactions were assessed using guinea pigs, and strong delayed erythema was seen with DNS-4NSBA, which bound most strongly with GSH, whereas weak delayed erythema was seen with DNS-4ABA, which did not bind with GSH. This suggests a correlation between GSH conjugate production and skin reactions. DNS-4HABA enzymatically bound with proteins in rat and guinea pig liver cytosol and microsomal fractions. The proteins that bound to DNS-4HABA were purified by HPLC and then subjected to N-terminal amino acid analysis. Ubiquitin (10 kDa) and fatty acid binding protein (30 kDa) were detected in the rat liver cytosol fraction; retinol-dehydrogenase (35 kDa) in the rat microsomal fraction; and glutathione-S-transferase B (mmu) (25 kDa) in the guinea pig liver cytosol fraction. When DNS-4HABA or DNS-4NSBA binds to proteins that play important roles in the body, unexpected adverse reactions may occur. Furthermore, by utilizing our technique using model compounds, it may be possible to identify the carrier proteins of various compounds, including pharmaceutical agents.

Paroxetine as a 5-HT neuroendocrine probe.

RATIONALE: Acute administration of 40 mg paroxetine (a selective serotonin reuptake inhibitor) reportedly increases plasma cortisol in human subjects. This suggests that paroxetine may be a useful tool to probe brain serotonin function. OBJECTIVE: To investigate a dose-response relationship for paroxetine administration, and to determine whether a lower dose of paroxetine is sufficient to increase plasma ACTH and cortisol. METHODS: Twenty subjects were tested on three occasions in a double-blind, cross-over design receiving: (a) placebo, (b) paroxetine 20 mg and (c) paroxetine 40 mg administered orally at 8.00 a.m. In addition, five of the 20 subjects received paroxetine 20 mg plus cyproheptadine (a 5-HT(2) receptor antagonist) 4 mg and four subjects were given paroxetine 40 mg plus cyproheptadine 4 mg in an open manner. Plasma ACTH and cortisol levels were measured prior to administration and every hour for 6 h thereafter. RESULTS: Paroxetine, particularly 20 mg rather than 40 mg, significantly increased plasma ACTH and cortisol. Paroxetine 40 mg but not 20 mg caused significantly more nausea than the placebo. Cyproheptadine attenuated ACTH and cortisol responses to 20 mg but not to 40 mg paroxetine. CONCLUSIONS: Low-dose (20 mg) paroxetine has greater potential utility than larger doses as a neuroendocrine challenge test. The endocrine responses to paroxetine are probably mediated at least partially by 5-HT(2A/2C) receptors.

cDNA cloning and expression of rat leukotriene C(4) synthase: elevated expression in rat basophilic leukemia-1 cells after treatment with retinoic acid.

Leukotriene C(4) synthase (LTC(4) S) is considered a pivotal enzyme for generation of potent proinflammatory mediators, cysteinyl-leukotrienes (cysLTs). LTC(4) S cDNA was cloned in rat basophilic leukemia-1 (RBL-1) cells, and exhibited 84.8% and 94.5% identity with the reported human and mouse LTC(4) S cDNA sequences, respectively. Homology between the rat LTC(4) S amino acid sequence and the corresponding sequences from the other species was 86.5% and 95.3% with human and mouse sequences, respectively. Rat LTC(4) S thus showed extensive homology with both mouse and human cDNA sequences. The active enzyme as assessed by LTC(4) S activity was expressed in COS-7 cells. While RBL-1 cells after the culture for 48 h in the presence of 0.1 microg/ml all trans -retinoic acid (RA) exhibited 27 times higher LTC(4) S activity than control cells, Northern-blot analysis of RA-treated cells showed upregulation of LTC(4) S mRNA. Polyclonal antibody was raised against the synthesized peptide deduced from the nucleotide sequence. Thus, Western-blot analysis of RBL-1 cells treated with RA and COS-7 cells transfected with pcDNA-LTC(4) S commonly showed a band at approximately 18 kDa in each solubilized enzyme solution, but either control cells did not. This cDNA probe and antibody may be useful for investigating the roles of cysLTs in various experimental models of rats.

Angiosarcoma of vagina successfully treated with interleukin-2 therapy and chemotherapy: a case report.

We report a case of angiosarcoma of the vagina in a 61-year-old woman who had undergone radical hysterectomy and pelvic irradiation for uterine cervical adenocarcinoma 14 years previously. Combination chemotherapy (cyclophosphamide, vincristine, doxorubicin and dacarbazine) and interleukin-2 induced complete remission of the tumor. The patient remained free from disease for 15 months.

Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.

Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 microM crocin. Moreover, crocin suppressed the TNF-alpha-induced expression of Bcl-Xs and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-X(L) mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-alpha-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.

Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the processes of peripheral tissue remodeling and fibrinolysis through the regulation of plasminogen activation. We found that cultured human astrocytes efficiently released PAI-1, and that both mRNA expression and protein release of PAI-1 were suppressed by pretreatment of the cells with daunorubicin. To examine the role of PAI-1 in the nervous system, neuronally differentiated PC-12 cells (PC-12 neurons) were maintained in a PAI-1-deficient culture medium derived from daunorubicin-pretreated astrocytes. The deficiency of PAI-1 in the medium caused a significant reduction in Bcl-2 and Bcl-XL mRNAs and an increase in Bcl-XS and Bax mRNAs in PC-12 neurons at 3 h. The changes in balance between mRNA expressions of the anti- and pro-apoptotic Bcl-2 family proteins caused caspase-3 activation following the release of cytochrome c from mitochondria. Apoptotic morphological change and DNA fragmentation were also observed in the neuronal cells at 24 h. Addition of exogenous PAI-1 protein to the inhibitor-deficient medium blocked the apoptotic changes in PC-12 neurons. However, addition of PAI-1 antibodies to control medium caused similar apoptotic changes in PC-12 neurons. During the apoptotic processes, plasminogen activator (PA) activity in the PAI-1-deficient medium was as low as the control level. The present data suggest that PAI-1 has physiological functions other than its role as PA inhibitor for the survival of neurons.

Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase.

A sphingomyelin analogue 2, in which the long alkenyl chain and the phosphodiester moiety of sphingomyelin were replaced by a phenyl and an isosteric difluoromethylenephosphonic acid, was prepared to evaluate its inhibitory potency to sphingomyelinase. The analogue non-competitively inhibited the neutral sphingomyelinase in bovine brain microsomes with an IC50 of 400 microM. The compound had the ability to suppress tumor necrosis factor alpha-induced apoptosis of PC-12 neurons at a low concentration of 0.1 microM.

Daunorubicin attenuates tumor necrosis factor-alpha-induced biosynthesis of plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.

The anthracycline antibiotic daunorubicin is reported to induce apoptosis in cells by triggering ceramide generation through de novo synthesis or sphingomyelin hydrolysis. Treatment of human umbilical vein endothelial cells (HUVEC) with daunorubicin markedly decreased the mRNA expression and protein release of plasminogen activator inhibitor-1 (PAI-1). This cellular event was accompanied by a significant increase in the total ceramide content in HUVEC. On the other hand, tumor necrosis factor (TNF)-alpha treatment of HUVEC led to an increase in both PAI-1 mRNA expression and protein release, and an enhancement of total ceramide content was also observed. The stimulating effect of TNF-alpha on PAI-1 synthesis was attenuated by the pretreatment of HUVEC with daunorubicin. Interestingly, the daunorubicin-induced increase in ceramide content was blocked by addition of the potent ceramide synthase inhibitor fumonisin B(1), while the TNF-alpha-induced ceramide increase was not affected by this drug. Fumonisin B(1) treatment restored the daunorubicin-induced decrease in PAI-1 release to approximately 70% of the control, but did not affect the TNF-alpha-induced increase in PAI-1 release. Thus, these data imply the possibility that the subcellular topology of ceramide production determines its lipid mediator function in the regulation of PAI-1 synthesis in HUVEC, because both TNF-alpha and daunorubicin could increase the ceramide levels.

Uterine angiomyolipoma: case report and review of the literature.

Extrarenal angiomyolipomas (AML) have been reported at various anatomical sites, but infrequently in the gynecological region. In the uterus, only a few cases have been described. We describe a uterine angiomyolipoma occurring in a 40-year-old woman without evidence of tuberous sclerosis. The tumor arose on the right wall of the uterine body and was partially cystic, and it was associated with marked degeneration. It was composed of mature adipose tissue, anomalous blood vessels and non-vascular smooth muscle cells. Immunohistochemistry revealed that non- vascular smooth muscle cells were positive for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, antihuman muscle actin (HHF35) and progesterone receptor (PR), and negative for cytokeratin, antihuman melanoma (HMB45), CD34, S-100 and estrogen receptor (ER). It is of particular interest that non-vascular smooth muscle cells were negative for HMB45, in contrast to renal and other extrarenal AML in which HMB45 immunoreactivity has been demonstrated in these cells.

Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide.

The present study underscores a regulatory role of intracellular ceramide in astrocytes for the release of an extracellular serine protease, tissue-type plasminogen activator (t-PA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Treatment of cultured human astrocytes with N-acetylsphingosine, a cell-permeable short-chain ceramide analogue or daunorubicin that could increase intracellular ceramide via activation of ceramide synthase or sphingomyelin hydrolysis increased the release of t-PA and conversely decreased the PAI-1 release. Interestingly, treatment of the astrocytes with tumor necrosis factor (TNF)-alpha also increased the intracellular ceramide levels but caused the elevation of PAI-1 release without altering the t-PA release. These data suggest that the generation of ceramide in astrocytes is linked at least with the regulation of PAI-1 release. We also demonstrate that the suppression of PAI-1 release with daunorubicin accelerates the cell death of neuronally differentiated PC12 cells and suggest an antiapoptotic role of PAI-1 in the nervous system.