Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study.

BACKGROUND: Growing evidence suggests that spiritual/religious involvement may have beneficial effects on both psychological and physical functions. However, the biological basis for this relationship remains unclear. This study explored the role of spiritual/religious involvement across a wide range of biological markers, including transcripts and metabolites, associated with the psychological aspects of empathy in Buddhist priests. METHODS: Ten professional Buddhist priests and 10 age-matched non-priest controls were recruited. The participants provided peripheral blood samples for the analysis of gene expression and metabolic profiles. The participants also completed validated questionnaires measuring empathy, the Health-Promoting Lifestyle Profile-II (HPLP-II), and a brief-type self-administered diet history questionnaire (BDHQ). RESULTS: The microarray analyses revealed that the distinct transcripts in the Buddhist priests included up-regulated genes related to type I interferon (IFN) innate anti-viral responses (i.e., MX1, RSAD2, IFIT1, IFIT3, IFI27, IFI44L, and HERC5), and the genes C17orf97 (ligand of arginyltranseferase 1; ATE1), hemoglobin γA (HBG1), keratin-associated protein (KRTAP10-12), and sialic acid Ig-like lectin 14 (SIGLEC14) were down-regulated at baseline. The metabolomics analysis revealed that the metabolites, including 3-aminoisobutylic acid (BAIBA), choline, several essential amino acids (e.g., methionine, phenylalanine), and amino acid derivatives (e.g., 2-aminoadipic acid, asymmetric dimethyl-arginine (ADMA), symmetric dimethyl-arginine (SMDA)), were elevated in the Buddhist priests. By contrast, there was no significant difference of healthy lifestyle behaviors and daily nutrient intakes between the priests and the controls in this study. With regard to the psychological aspects, the Buddhist priests showed significantly higher empathy compared with the control. Spearman's rank correlation analysis showed that empathy aspects in the priests were significantly correlated with the certain transcripts and metabolites. CONCLUSIONS: We performed in vivo phenotyping using transcriptomics, metabolomics, and psychological analyses and found an association between empathy and the phenotype of Buddhist priests in this pilot study. The up-regulation of the anti-viral type I IFN responsive genes and distinct metabolites in the plasma may represent systemic biological adaptations with a unique signature underlying spiritual/religious practices for Buddhists.

Low serum eicosapentaenoic acid level is a risk for ventricular arrhythmia in patients with acute myocardial infarction: a possible link to J-waves.

Eicosapentaenoic acid (EPA) has antiarrhythmic effects. The J-wave on an electrocardiogram is associated with a high incidence of ventricular tachycardia/fibrillation (VT/VF). We evaluated relationships between EPA and J-waves, and their involvement in the occurrence of VT/VF in acute myocardial infarction (AMI). Two hundred consecutive patients undergoing successful percutaneous coronary intervention within 12 h after AMI onset were enrolled. Serum EPA level and J-waves at admission were evaluated. The patients were divided into two groups according to the optimal cutoff value (2.94) of serum EPA level (% of total fatty acids): LOW (<2.94, 61 ± 11 years, n = 103) and HIGH groups (≥2.94, 70 ± 13 years, n = 81). J-waves were observed more frequently in the LOW (36/103, 35 %) than in HIGH group (16/81, 20 %) (P = 0.020). The 30-day incidence of VT/VF including those occurring before admission was higher in the LOW (19.5 %) than in HIGH group (6.2 %) (P = 0.009). The patients with J-waves showed a higher incidence of VT/VF (23.1 %) than those without J-waves (9.9 %) (P = 0.019). Kaplan-Meier analysis showed that the highest incidence of VT/VF was observed in the LOW with J-wave group (27.8 %), followed by the LOW without J-wave (15.0 %), HIGH with J-wave (12.5 %), and HIGH without J-wave (4.6 %) (P = 0.013). Cox proportional hazard analysis revealed that Killip grade and low serum EPA level or presence of J-waves were significantly associated with the incidence of VT/VF. Low serum EPA level is a risk for incidence of VT/VF in the acute phase of myocardial infarction. Involvement of the J-wave and its possible link with EPA in the pathogenesis of ischemia-induced VT/VF are suggested.

Sense of Coherence as a Mediator in the Association Between Empathy and Moods in Healthcare Professionals: The Moderating Effect of Age.

While empathy is considered a critical determinant of the quality of medical care, growing evidence suggests it may be associated with both one's own positive and negative moods among healthcare professionals. Meanwhile, sense of coherence (SOC) plays an essential role in the improvement of both psychological and physical health. Reportedly, individual SOC reaches full stability after around age 30. The aim of this study was first to evaluate the mediatory role of SOC on the association between empathy and individual moods among 114 healthcare professionals in a general hospital, and then to examine the moderating effect of age on this association. Participants completed a range of self-report demographic questionnaires, Empathy Process Scale (EPS), the 13-item Antonovsky's SOC, and Profile of Mood States (POMS). Findings showed that SOC mediated the relations between empathy (EPS) and both POMS-Vigor (POMS-V: self-vigor mood) and POMS-Depression (POMS-D: self-depression mood). Notably, moderated mediation analysis revealed that there was a significant interaction (age × SOC) on self-vigor mood (POMS-V) in healthcare professionals. The indirect effect of empathy (EPS) on self-vigor mood (POMS-V) through SOC was significant at over mean age "32.83." Although there was no significant interaction with age regarding the indirect effect of empathy (EPS) on self-depression mood (POMS-D), in the sub-category level analysis of empathy (EPS), we found a significant interaction item [age × empathy for other's negative affect (EPS-N)] on SOC. This indirect effect was also significant at over mean age "32.83." Taken, together, the current study highlighted the significant mediator of SOC on that empathy amplifies self-vigor mood and attenuates self-depression mood as a protective factor among the Japanese healthcare professionals. Some components of these processes may depend on the moderating role of age, indicating that we may need to consider the SOC development with age for more effective empathy performance interventions among healthcare professionals.

Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis?

The objective of this study was to evaluate the utility of the determination of adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in Japan, a country with intermediate incidence of tuberculosis (TB). We retrospectively reviewed the clinical records of 435 patients with pleural effusion and investigated their pleural ADA levels as determined by an auto analyzer. ROC analysis was also performed. The study included patients with MPE (n＝188), TPE (n＝124), benign nontuberculous pleural effusion (n＝94), and pleural effusion of unknown etiology (n＝29). The median ADA level in the TPE group was 70.8U/L, which was significantly higher than that in any other groups (p＜0.05). The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As many as 9% of patients with lung cancer and 15% of those with mesothelioma were false-positive with this ADA cutoff setting. Although the ADA activity in pleural fluid can help in the diagnosis of TPE, it should be noted that some cases of lung cancer or mesothelioma show high ADA activity in geographical regions with intermediate incidence of TB, in contrast to high prevalence areas.

[An elderly case of hyperglycemic hyperosmolar syndrome with hyperketonemia].

A 72-year-old man had been treated for type 2 diabetes mellitus and gastric cancer. He had been receiving insulin and chemotherapy because of diabetes mellitus and terminal gastric cancer. The dose of insulin was decreased due to the appetite loss, but his general condition deteriorated with disturbed consciousness (JCS I-3), so he was admitted to our hospital in November 2006. On admission, he showed abnormal laboratory data such as WBC 11,070/microl, Hb 10.2 g/dl, serum BUN 64.1 mg/dl, serum Cr 2.23 mg/dl, serum CRP 16.78 mg/dl, plasma glucose 830 mg/dl, serum osmolarity 360 mOsm/l, and serum total keton body 5,490 micromol/l. However, serum Na (142 mEq/l), serum K (4.5 mEq/l), arterial blood pH (7.368), and the anion gap (15 mEq/l) were within the normal range. He was given a diagnosis of hyperglycemic hyperosmolar syndrome with hyperketonemia. Immediately treatment was started with physiologic saline and regular insulin infusion. After treatment, glucose level and serum osmolarity ameliorated. Though elderly cases with hyperglycemic hyperosmolar syndrome and hyperketonemia are rarely reported, it is important to be aware that elderly patients often have very atypical signs and symptoms. We report this case to show diverse nature of elderly patients.

Renin-angiotensin system research: from molecules to the whole body.

Hypertension is one of the most important risk factors and a leading cause of death from cardiovascular and cerebrovascular diseases. Based on numerous previous studies, hypertension is thought to be caused by the complex mutual interactions of genetic factors and environmental factors, such as excessive salt intake and stress. However, its detailed mechanisms are not yet clearly understood. The renin-angiotensin system (RAS) is a key hormonal system in the pathogenesis of hypertension. New knowledge is still accruing on this cascade, even after more than 120 years since the discovery of renin. To clarify the molecular mechanisms of RAS in vivo, we created transgenic mice with chronic hypertension. These mice carry the human genes encoding renin, a hypertensive enzyme, and its substrate angiotensinogen. Hypotensive mice homozygous for a targeted disruption of the angiotensinogen gene were also created. This review presents our 47-year history of RAS research.

Laughter modulates prorenin receptor gene expression in patients with type 2 diabetes.

OBJECTIVE: The purpose of this study was to assess whether laughter influences the expression of the receptor gene for prorenin that participates in the progression of diabetic nephropathy. METHODS: Sixteen normal subjects and 23 patients with type 2 diabetes [12 nephropathy (-) and 11 nephropathy (+)] were recruited to examine the effects of laughter on the modulation of prorenin receptor gene expression. After watching a comedy show, laughter-induced changes in the levels of blood prorenin and the expression of prorenin receptor gene were analyzed by an antibody-activating direct enzyme kinetic assay and by reverse transcriptase polymerase chain reaction, respectively. RESULTS: In diabetic patients, laughter decreased the level of blood prorenin [93.4-60.4 ng/l in nephropathy (-) patients, 196.6-166.7 ng/l in nephropathy (+) patients] and up-regulated the prorenin receptor gene [1.49-fold in nephropathy (-) patients, 1.46-fold in nephropathy (+) patients]. No significant changes in the expression of this gene were recognized in normal subjects. CONCLUSION: The beneficial effects of laughter on preventing the exacerbation of diabetic nephropathy are strongly suggested in terms of normalizing the expression of the prorenin receptor gene followed by reducing the level of blood prorenin.

Enhanced transient receptor potential channel-mediated Ca2+ influx in the cells with phospholipase C-δ1 overexpression: its possible role in coronary artery spasm.

We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca2+ influx and its underlying mechanisms. We used human embryonic kidney (HEK)-293 and coronary arteries smooth muscle cells (CASMC). Intracellular free Ca2+ concentration ([Ca2+ ]i ; nm) was measured by fura-2, and Ca2+ influx was evaluated by the increase in [Ca2+ ]i after addition of extracellular Ca2+ . Acetylcholine (ACh) was used to induce Ca2+ influx. ACh-induced peak Ca2+ influx was 19 ± 3 in control HEK-293 cells and 71 ± 8 in the cells with PLC-δ1 overexpression (P < 0.05 between two groups). Nifedipine partially suppressed this Ca2+ influx, whereas either 2-APB or knockdown of classical transient receptor potential channel 6 (TRPC6) blocked this Ca2+ influx. In the human CASMC, ACh-induced peak Ca2+ influx was 29 ± 6 in the control and was increased to 45 ± 16 by PLC-δ1 overexpression (P < 0.05). Like HEK-293 cells, pretreatment with nifedipine partially suppressed Ca2+ influx, whereas either 2-APB or knockdown of TRPC6 blocked it. ACh-induced Ca2+ influx was enhanced by PLC-δ1 overexpression, and was blocked partially by nifedipine and completely by 2-APB. TRPC-mediated Ca2+ influx may be related to the enhanced Ca2+ influx in PLC-δ1 overexpression.

The effect of losartan and amlodipine on serum adiponectin in Japanese adults with essential hypertension.

BACKGROUND: Adiponectin, an adipocyte-derived protein, is reduced in patients with hypertension and insulin resistance (IR). Angiotensin II receptor blockers (ARBs) have been reported to improve IR and reduce albuminuria. The purpose of this study was to evaluate the influence of an ARB and a calcium channel blocker on serum adiponectin levels in Japanese patients with hypertension who were treated with losartan or amlodipine for 3 months. METHODS: Patients with essential hypertension (EHT) were randomized to treatment prospectively with losartan (50-100 mg/d) or amlodipine (5-10 mg/d) for 3 months. Patients with renal damage and/or macroproteinuria were excluded. The urine albumin/creatinine ratio, homeostasis model assessment (HOMA) index, adiponectin concentration, and tumor necrosis factor-alpha (TNF-alpha) concentration of each patient were evaluated before and after 3 months of treatment. When the HOMA index exceeded 1.73, a patient was considered to have IR. RESULTS: All 40 participants completed both 3-month treatment periods. Study patients were primarily male (52.5%) with a mean (SD) age of 63.8 (10.6) years and a mean body weight of 60.7 (10.8) kg. Patients with EHT and diabetes mellitus (n = 9) and IR (n = 12) had significantly lower adiponectin concentrations than patients who had EHT without diabetes or IR (n = 19; mean [SD], 7.84 [5.54] vs 12.81 [7.36] microg/mL, P = 0.034; and 6.12 [3.04] vs 12.81 [7.36] microg/mL, P = 0.004, respectively). Adiponectin concentrations correlated negatively with body mass index (r = -0.393; P = 0.012) and HOMA index (r = -0.440; P = 0.005) and positively with high-density lipoprotein cholesterol (r = 0.441; P = 0.004) before treatment. Systolic blood pressure was significantly decreased in patients treated with losartan (n = 20; mean [SD], 166 [19] to 140 [15] mm Hg; P < 0.001) or amlodipine (n = 20; 164 [15] to 136 [15] mmHg; P < 0.001), and diastolic blood pressure also was significantly decreased with losartan (93 [14] to 83 [10] mm Hg; P = 0.031) or amlodipine (96 [12] to 82 [10] mm Hg; P < 0.001). Losartan increased adiponectin concentrations (9.56 [6.75] to 10.36 [6.94] microg/mL; P = 0.038), whereas amlodipine had no significant effect (9.67 [6.62] to 10.01 [6.79] microg/mL). The difference in TNF-alpha concentration before and after treatment with losartan and amlodipine did not reach statistical significance (mean [SD], 15.2 [1.4] to 14.8 [1.5] pg/mL; and 14.3 [1.4] to 14.5 [1.7] pg/mL, respectively). CONCLUSION: In this study, Japanese adults with EHT had significant increases in adiponectin after 3 months of treatment with 50 to 100 mg/d of losartan, but not with 5 to 10 mg/d of amlodipine.

Laughter therapy modulates the parameters of renin-angiotensin system in patients with type 2 diabetes.

The effect of laughter therapy on the plasma levels of renin, angiotensinogen, and prorenin was investigated in patients with type 2 diabetes. In the diabetic patients, the mean plasma renin concentrations were 24.6+/-12.1 ng/ml/h in the first observation (at the beginning of laughter therapy), 8.2+/-3.4 ng/ml/h in the second observation (three months after the beginning of laughter therapy) and 7.7+/-1.7 ng/ml/h in the third observation (six months after the beginning of laughter therapy). The mean plasma angiotensinogen concentrations in the 1st, 2nd and 3rd observations were 0.19+/-0.08, 0.47+/-0.12, 0.42+/-0.14 microg/ml, respectively. The mean plasma prorenin concentrations in the 1st, 2nd and 3rd observations during the laughter therapy were 195.1+/-66.2, 193.4+/-88.2 and 170.7+/-52.5 pg/ml, respectively. Plasma renin concentrations were significantly decreased (p<0.05) by the therapy. Subnormal concentrations of plasma angiotensinogen were found in the 1st observation and increased significantly (p<0.05) to the normal range after the therapy. Plasma prorenin concentration only slightly changed during the laughter therapy. Other biochemical parameters remained unchanged during the laughter therapy. These results indicated that a long-term laughter therapy changed the plasma components of renin-angiotensin system in patients with diabetes. Thus, laughter therapy can be used as non-pharmacological treatment for the prevention of diabetic microvascular complications.

Non-coding RNAs and hypertension-unveiling unexpected mechanisms of hypertension by the dark matter of the genome.

Hypertension is a major risk factor of cardiovascular diseases and a most important health problem in developed countries. Investigations on pathophysiology of hypertension have been based on gene products from coding region that occupies only about 1% of total genome region. On the other hand, non-coding region that occupies almost 99% of human genome has been regarded as "junk" for a long time and went unnoticed until these days. But recently, it turned out that noncoding region is extensively transcribed to non-coding RNAs and has various functions. This review highlights recent updates on the significance of non-coding RNAs such as micro RNAs and long non-coding RNAs (lncRNAs) on the pathogenesis of hypertension, also providing an introduction to basic biology of noncoding RNAs. For example, microRNAs are associated with hypertension via neuro-fumoral factor, sympathetic nerve activity, ion transporters in kidneys, endothelial function, vascular smooth muscle phenotype transformation, or communication between cells. Although reports of lncRNAs on pathogenesis of hypertension are scarce at the moment, new lncRNAs in relation to hypertension are being discovered at a rapid pace owing to novel techniques such as microarray or next-generation sequencing. In the clinical settings, clinical use of non-coding RNAs in identifying cardiovascular risks or developing novel tools for treating hypertension such as molecular decoy or mimicks is promising, although improvement in chemical modification or drug delivery system is necessary.

Studies of 1-Amino-2,2-difluorocyclopropane-1-carboxylic Acid: Mechanism of Decomposition and Inhibition of 1-Aminocyclopropane-1-carboxylic Acid Deaminase.

1-Amino-2,2-difluorocyclopropane-1-carboxylic acid (DFACC) is of interest in the study of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase due to the increased reactivity of its cyclopropyl functionality. It is shown that DFACC is unstable under near-physiological conditions where it primarily decomposes via specific-base catalysis to 3-fluoro-2-oxobut-3-enoic acid with a rate constant of 0.18 ± 0.01 min(-1). Upon incubation with ACC deaminase, DFACC is found to be a slow-dissociating inhibitor of ACC deaminase with submicromolar affinity.

Transcriptional profiling of genes responsive to abscisic acid and gibberellin in rice: phenotyping and comparative analysis between rice and Arabidopsis.

We collected and completely sequenced 32,127 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. "Nipponbare." Mapping of these clones to genomic DNA revealed approximately 20,500 transcriptional units (TUs) in the rice genome. For each TU, we selected 60-mers using an algorithm that took into account some DNA conditions such as base composition and sequence complexity. Using in situ synthesis technology, we constructed oligonucleotide arrays with these TUs on glass slides. We targeted RNAs prepared from normally grown rice callus and from callus treated with abscisic acid (ABA) or gibberellin (GA). We identified 200 ABA-responsive and 301 GA-responsive genes, many of which had never before been annotated as ABA or GA responsive in other expression analysis. Comparison of these genes revealed antagonistic regulation of almost all by both hormones; these had previously been annotated as being responsible for protein storage and defense against pathogens. Comparison of the cis-elements of genes responsive to one or antagonistic to both hormones revealed that the antagonistic genes had cis-elements related to ABA and GA responses. The genes responsive to only one hormone were rich in cis-elements that supported ABA and GA responses. In a search for the phenotypes of mutants in which a retrotransposon was inserted in these hormone-responsive genes, we identified phenotypes related to seed formation or plant height, including sterility, vivipary, and dwarfism. In comparison of cis-elements for hormone response genes between rice and Arabidopsis thaliana, we identified cis-elements for dehydration-stress response as Arabidopsis specific and for protein storage as rice specific.

Comprehensive analysis of NAC family genes in Oryza sativa and Arabidopsis thaliana.

The NAC domain was originally characterized from consensus sequences from petunia NAM and from Arabidopsis ATAF1, ATAF2, and CUC2. Genes containing the NAC domain (NAC family genes) are plant-specific transcriptional regulators and are expressed in various developmental stages and tissues. We performed a comprehensive analysis of NAC family genes in Oryza sativa (a monocot) and Arabidopsis thaliana (a dicot). We found 75 predicted NAC proteins in full-length cDNA data sets of O. sativa (28,469 clones) and 105 in putative genes (28,581 sequences) from the A. thaliana genome. NAC domains from both predicted and known NAC family proteins were classified into two groups and 18 subgroups by sequence similarity. There were a few differences in amino acid sequences in the NAC domains between O. sativa and A. thaliana. In addition, we found 13 common sequence motifs from transcriptional activation regions in the C-terminal regions of predicted NAC proteins. These motifs probably diverged having correlations with NAC domain structures. We discuss the relationship between the structure and function of the NAC family proteins in light of our results and the published data. Our results will aid further functional analysis of NAC family genes.

Genomics approach to abscisic acid- and gibberellin-responsive genes in rice.

We used an 8987-EST collection to construct a cDNA microarray system with various genomics information (full-length cDNA, expression profile, high accuracy genome sequence, phenotype, genetic map, and physical map) in rice. This array was used as a probe to hybridize target RNAs prepared from normally grown callus of rice and from callus treated for 6 hr or 3 days with the hormones abscisic acid (ABA) or gibberellin (GA). We identified 509 clones, including many clones that had never been annotated as ABA-or GA-responsive. These genes included not only ABA- or GA-responsive genes but also genes responsive to other physiological conditions such as pathogen infection, heat shock, and metal ion stress. Comparison of ABA- and GA-responsive genes revealed antagonistic regulation for these genes by both hormones except for one defense-related gene, thionin. The gene for thionin was up-regulated by both hormone treatments for 3 days. The upstream regions of all the genes that were regulated by both hormones had cis-elements for ABA and GA response. We performed a clustering analysis of genes regulated by both hormones and various expression profiles that showed three notable clusters (seed tissues, low temperature and sugar starvation, and thionin-gene related). A comparison of the cis-elements for hormone response genes between rice and Arabidopsis thaliana, we identified cis-elements for dehydration-stress response or for expression of amylase gene as Arabidopsis gene-specific or rice gene-specific, respectively.

A novel feature of microsatellites in plants: a distribution gradient along the direction of transcription.

A computer-based analysis was conducted to assess the characteristics of microsatellites in transcribed regions of rice and Arabidopsis. In addition, two mammals were simultaneously analyzed for a comparative analysis. Our analyses confirmed a novel plant-specific feature in which there is a gradient in microsatellite density along the direction of transcription. It was also confirmed that pyrimidine-rich microsatellites are found intensively near the transcription start sites, specifically in the two plants, but not in the mammals. Our results suggest that microsatellites located at high frequency in the 5'-flanking regions of plant genes can potentially act as factors in regulating gene expression.

Relative abundance and patterns of correlation among six cytokines in pleural fluid measured by cytometric bead array.

Several cytokines play significant roles in the development and pathogenesis of pleural effusion. Little is known, however, about possible interactions between individual cytokines in terms of regulation of their relative abundance in the effusion. We studied 93 patients presenting with pleural effusion to the National Sanyo Hospital (68 men and 25 women; mean age, 64 years). Twenty-two patients had tuberculous pleurisy, 40 had malignant pleuritis, and 31 had effusions due to an etiology other than tuberculosis or cancer (miscellaneous). Pleural fluid concentrations of IL-2, IL-4, IL-5, IL-10, TNF-alpha, and INF-gamma were simultaneously measured by cytometric bead array (CBA). The ratios of IL-4/IL-5, IL-4/TNF-alpha, IL-2/TNF-alpha, and IL-10/TNF-alpha were lower in patients with tuberculosis pleurisy compared with other patients. In all three groups of patients significant correlation was seen between abundance of IL-2 vs. IL-4, IL-5, IL-10, or TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In malignant pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, TNF-alpha, or INF-gamma, between IL-4 vs. INF-gamma, and between TNF-alpha vs. INF-gamma. In tuberculosis pleural fluid patients, the significant correlation was between IL-2 vs. TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In miscellaneous pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, IL-10, or TNF-alpha, between IL-4 vs. IL-10, TNF-alpha, and between IL-10 vs. TNF-alpha. No significant correlation was observed between other pairs of cytokines. Strong correlation in abundance between particular cytokines in pleural fluids suggests cross-talk between them, in terms that an altered level of one of them provides a feedback mechanism regulating synthesis and/or secretion of another one. Such interactions may play important roles in pathogenesis and severity of the effusion. The CBA methodology provides a convenient tool to investigate these interactions.

Malignant fibrous histiocytoma of the lung.

Primary malignant fibrous histiocytoma (MFH) of the lung is very rare. To date, only 32 reports of 63 cases of primary MFH of the lung have appeared in English, excluding tumors arising from the pulmonary arteries and pleura. We describe a patient with primary MFH of the lung who developed brain metastasis and involvement of pulmonary great vessels. In addition, we reviewed previously reported cases to establish the clinical characteristics and most appropriate management of primary pulmonary MFH. When disease is sufficiently limited, complete resection remains the mainstay of treatment.

[Rifampicin-induced severe thrombocytopenia in a patient with miliary tuberculosis].

A 74-year-old female visited a local clinic complaining of fever on January 21, 2002. A chest X-ray and a chest computed tomography (CT) showed diffuse micronodules in all lung fields, which strongly suggested miliary tuberculosis. On January 23, she was referred to our hospital for further examinations. Though sputum was negative on smear, culture, and polymerase chain reaction (PCR) for M. tuberculosis, bone marrow aspirate examined on admission revealed epithelioid granuloma. Therefore we diagnosed her as a miliary tuberculosis, and she was treated with 300 mg of Isoniazid (INH), 450 mg of Rifampicin, and 750 mg of Streptomycin (SM) daily. Five days later, severe thrombocytopenia (platelet count 0.3 x 10(4)/microliter) was observed. We immediately discontinued all antituberculous drugs and administered concentrated platelets and immune globulin. Platelet-associated IgG was detected, and megakaryocytes were slightly increased in moderately hypocellular marrow on the bone marrow aspirate examined again after the appearance of thrombocytopenia. Eleven days after discontinuing all antituberculous drugs, platelet count recovered to 10.2 x 10(4)/microliter. INH, SM, Levofloxacin (LV) were administered afterward, and these drugs did not induce thrombocytopenia. Though challenge administration of RFP was not performed, we concluded that the thrombocytopenia was immunologically induced by RFP. We should keep in mind that RFP-induced thromobocytopenia could appear in the first week after the initiation of therapy.

Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation.

Social interactions during adolescence are important especially for neuronal development and behavior. We recently showed that positive emotions induced by repeated tickling could modulate fear-related behaviors and sympatho-adrenal stress responses. In the present study, we examined whether tickling during early to late adolescence stage could reverse stress vulnerability induced by socially isolated rearing. Ninety-five male Fischer rats were reared under different conditions from postnatal day (PND) 21 to 53: group-housed (three rats/cage), isolated-nontickled (one rat/cage) and isolated-tickled (received tickling stimulation for 5min a day). Auditory fear conditioning was then performed on the rats at PND 54. Isolated-tickled rats exhibited significantly lower freezing compared with group-housed rats in the first retention test performed 48h after conditioning and compared with isolated-nontickled rats in the second retention test performed 96h after conditioning. Moreover, group-housed and isolated-tickled rats tended to show a significant decrease in freezing responses in the second retention test; however, isolated-nontickled rats did not. In the Morris water maze task that was trained in adulthood (PND 88), but not in adolescence (PND 56), isolated-nontickled rats showed slower decrease of escape latency compared to group-housed rats; however, tickling treatment significantly improved this deficit. These results suggest that tickling stimulation can alleviate the detrimental effects of isolated rearing during adolescence on fear responses and spatial learning.