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This article aims to formulate the relation between culture and society from the perspective of Niklas Luhmann’s theory of self-referential social systems. Traditional sociological theories, such as those proposed by Talcott Parsons and Alfred Schutz, consider the social to be based on a common culture among people. This idea posits that a society must be defined as a society of culture because it is a product of culture. Conversely, the theory of self-referential social systems does not presuppose such a common basis for the social. Even without a shared culture, a social system always emerges based on mutual intransparency (i. e., double contingency among people) and subsequently begins to control itself by remembering and forgetting the memory of its own operations. This memory is called culture, and it results from self-referential system operations. Therefore, as a product of the social system, culture can be described as a culture of a social system. This formulation is also applicable to the de-nationalized and de-territorialized world society. The world culture, or the culture of society, means contingency. As the eigenvalue of the world society, contingency gives the orientation of the further system-differentiation to the world society. Consequently, by placing the social before the cultural, a theoretical framework can be established for describing and analyzing the current world situation, in which cultures are being differentiated with many associated issues.

When Thomas Luckmann, a pioneer of the “linguistic turn” in sociology, regarded Émile Durkheim as a source for the sociology of language, he had lifeworldly community–building in mind. However, the French sociologist himself understood language in the context of civil society–building. To Durkheim, language was a “social thing in the highest degree” that enabled general ideas and intermediated them to people. Abstract human ideals like the civil religion since the French Revolution could be shared through (a common) language. Thus, Durkheim took the exclusive use of French in the Third Republic’s laic public education for granted, ignoring the patois in the country: This “child of the Enlightenment” considered French to be a universal language of Gesellschaft and, beyond ethno-communal elements, to work as a basis for the organic solidarity of French national civil society where the social division of labor was progressing. Durkheim’s theory was predicated on civil-linguistic, not ethnolinguistic, nationalism.

The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells.

Aim While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli. Methods We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors' faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants. Results Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition. Conclusion Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

This article clarifies the relationship between individual freedom and social order by relying on Niklas Luhmann’s social systems theory and thereby defines sociology’s contribution to social evolution as sociological enlightenment, which seeks otherwiseness in living experience and action. For this purpose, Luhmann’s theory will specifically be compared with Emile Durkheim’s and Alfred Schutz’s sociological theories. Durkheim, a “child of the Enlightenment,” considered freedom a collective ideal of moral individualism and conceived that the rational state realizes freedom by spreading the civil-religious human ideal for modern social order. In contrast, Schutz, following Henri Bergson, who criticized rationality for spatially fixing inner time, regarded freedom as a given in the individual’s underlying duration, not as a shared ideal. Yet, unlike Bergson, he continued relying on rationalism, and he thought that the sociological observer observes how something appears to people with the epoché of natural attitude, not what it objectively is. Inheriting this phenomenological subjectivism, Luhmann showed that the self-referentiality of consciousness also applies to society: A social system, which path-dependently emerges itself from a double contingency, observes the world in its own way based on its self-referentially constituted eigen-time. On account of this system closure, and contrary to Durkheim’s illuminist belief, there is no controlling entity in a highly evolved society, where freedom results from the enlarged, diversified possibilities of living experience and action (contingency). Thus, sociological enlightenment doubts self-evidence so that society brackets the taken-for-granted social order or social reality and amplifies individuals’ deviations to evolve toward freedom.

When Thomas Luckmann, a pioneer of the “linguistic turn” in sociology, regarded Émile Durkheim as a source for the sociology of language, he had lifeworldly community–building in mind. However, the French sociologist himself understood language in the context of civil society–building. To Durkheim, language was a “social thing in the highest degree” that enabled general ideas and intermediated them to people. Abstract human ideals like the civil religion since the French Revolution could be shared through (a common) language. Thus, Durkheim took the exclusive use of French in the Third Republic’s laic public education for granted, ignoring the patois in the country: This “child of the Enlightenment” considered French to be a universal language of Gesellschaft and, beyond ethno-communal elements, to work as a basis for the organic solidarity of French national civil society where the social division of labor was progressing. Durkheim’s theory was predicated on civil-linguistic, not ethnolinguistic, nationalism.

Methodological nationalism in sociological theory is unfit for the current globalized era, and should be discarded. In light of this contention, the present article discusses Max Weber’s view of language as a way to relativize the frame of the national society. While a “linguistic turn” in sociology since the 1960s has assumed that the sharing of language—linguistic community—stands as an intersubjective foundation for understanding of meaning, Weber saw linguistic community as constructed. From Weber’s rationalist, subjectivist, individualist viewpoint, linguistic community was a result of social actions, not a prior entity as assumed by German metaphysical organicism (and historicist holism). Indeed, Central Europe in Weber’s era was a battlefield of linguistic nationalism(s); in contrast to the national societies of the Cold War period, national borders were unstable and ultimately the multiethnic empires of the region were dismantled after World War I into ethnolinguistic nation-states. Experience of this contemporary reality brought Weber to the core of the relationship between language and politics: A language community is an imaginary one demarcated not by language itself but by conscious opposition against outsiders, with monolingual contexts within borders created artificially by homogenizing policies like linguistic standardization and national education—the first modernity of language. In this way, Weber felt, language can be a means to domination.

This paper aims to clarify the proper position of time as sociology’s basic concept in relation to meaning ( Sinn). In sociology, the inseparable relationship between time and meaning has been clearly shown by Schutz’s phenomenological sociology and Luhmann’s social systems theory. Referring to the respective theories of Bergson and Husserl, Schutz argued that the problem of meaning in Weber’s interpretative sociology is a problem of time. The meaning of an action that an actor subjectively thinks of is determined not by a common normative value for example, but rather through her/his own inner time: the meaning of an ongoing action ( Handeln) is the act ( Handlung) projected as an aim in the stream of consciousness. Similarly, Luhmann considered self-referential social systems as temporal subjects that cognize their own reality of the external world. Phenomena appearing to a social system through communicative intentionality are weighted by the system’s own past and future, and are thereby selectively (not randomly) actualized as meaningful units in the present. System order (or social order) is thus temporally organized in the atemporal, chaotic world of meaning. “Self-reference” is to refer to a system’s own eigen time ( Eigenzeit), which provides the basis for a system’s autonomy or freedom.

Objective The aim of this post hoc analysis was to evaluate which specific depressive items could predict subsequent durable recovery in patients with bipolar depression. Methods The study population was at least 18 years old and met DSM-IV criteria for a major depressive episode associated with either bipolar I or II disorder. The data were derived from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), in which patients with bipolar depression were randomly assigned to treatment for acute depression with a mood stabilizer plus an adjunctive antidepressant drug or placebo. The primary and secondary outcomes were durable recovery (ie, 8 consecutive weeks of euthymia) and treatment-emergent affective switch (ie, transition to mania or hypomania), respectively. Binary logistic regression analysis was performed to identify specific symptoms whose improvement during the first 2 weeks predicted those outcomes; the score change of each individual symptom in the continuous symptom subscales for depression (SUM-D) from week 0 to week 2 was used as an independent variable. Results In the evaluable 188 participants who took placebo and active drugs, the improvement in loss of self-esteem (P = .037) or loss of energy (P = .040) at week 2 was significantly associated with higher chances of subsequent durable recovery. For participants taking active drugs (n = 91), solely the improvement in loss of energy at week 2 was significantly associated with subsequent durable recovery (P = .027). There was a significant association between the improvement of psychomotor retardation at week 2 and subsequent affective switch (P = .008). Conclusions These findings imply that focusing on individual symptoms is important in bipolar depression, rather than relying solely on a summed score in rating scales. Trial registration The original STEP-BD dataset is registered on ClinicalTrials.gov (identifier: NCT00012558).

The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells.

[Objective] To determine whether three sputum examinations with fluorescent staining are necessary to diag- nose tuberculosis (TB) in our hospital. [Patients] From April 2005 to December 2012, 379 TB patients were admitted and received anti-TB therapy in our hospital. [Methods] A retrospective study was conducted to assess the positivity rates of sputum smears based on three exami- nations. The positivity rate of first sputum smear and the cumulative smear-positive rates in the second and third were determined. Then, we also determined difference of positivity rates in sputum properties, sampling procedures and cavity formation. [Results] Of the 379 patients who met the screening criteria, 300 tested positive based on the first sputum smear (79.2%). The positivity rate of the first sputum smears was higher in the purulent sputum group than in the mucous sputum group (91.2% vs. 72.3%). Cavity formation, and sputum extraction procedures were not related to the positivity rate of the first sputum smears. In the mucous sputum group, the cumulative smear-positive rate in the second test significantly rose, but did not rise in the third test. [Conclusions] Three sputum smear examinations were necessary in patients who submitted mucous sputum samples. It is important to get purulent sputum.

Objectives To prevent the onset of lifestyle-related diseases associated with metabolic syndrome (MetS) in Japan, research into the development of a useful screening method is strongly desired. We developed a new screening questionnaire (JAMRISC) utilizing a logistic regression model and evaluated its ability to predict the development of MetS, type 2 diabetes and other lifestyle-related diseases in Japanese populace. Methods JAMRISC questionnaire was sent to 1,850 individuals in Rumoi, a small city in Hokkaido. We received a total of 1,054 valid responses. To maximize the target individuals accurately diagnosed with MetS, logistic regression analysis was used to generate a unique metabolic syndrome score calculation formula as taking into consideration the clinical relevance of each question item as individual coefficients. Results The results of our comparative research utilizing both JAMRISC and Finnish Diabetes Risk Score (FINDRISC) questionnaires revealed the usefulness of JAMRISC for its ability to detect risks for MetS, pre-MetS, diabetes, and pre-diabetes. Study of disease risk detection via JAMRISC questionnaire targeting the 4283 residents of Rumoi indicated a high detection rate for pre-MetS (98.8 %), MetS (94.2 %), pre-diabetes (85.1 %) and type 2 diabetes (94.9 %). In addition, JAMRISC was useful not only as a MetS risk score test, but also as a screening tool for diagnosing insulin resistance. Conclusions JAMRISC questionnaire is a useful instrument for the detection of early risk of not only MetS and type 2 diabetes but also insulin resistance.

A Correction to this paper has been published: 10.1007/s11186-021-09436-2

While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli.We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors' faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants.Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition.Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

The aim of this study is to evaluate whether an adjunct antidepressant therapy at a higher dose to a mood stabilizer would make a difference in the treatment of bipolar depression. This is a post-hoc analysis of the data from the randomized treatment for acute depression of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), in which patients with bipolar depression were randomly assigned to treatment with a mood stabilizer plus adjunctive antidepressant drugs or placebo. According to the highest dose received in the course of treatment, the subjects were divided into one of the following three groups: high-dose, low-dose and placebo groups. The primary and secondary outcomes were durable recovery (which was operationally defined as eight consecutive weeks with/ = 2 symptoms) and treatment-emergent affective switch (i.e. transition to mania or hypomania), respectively. In the evaluable 333 subjects, subjects in both the high-dose (n = 102) and placebo groups (n = 169) more significantly achieved durable recovery than the low-dose group (n = 62) (odds ratio = 3.013 [p = 0.009], 2.899 [p = 0.008], respectively). No significant association was found between the dose status and treatment-emergent affective switch (p = 0.614). The allocation to either high- and low-dose antidepressants was not randomized and the dose was guided by a case-by-case decision, which hampers to draw a firm conclusion on dose-response issues and renders the findings as preliminary. Nevertheless, higher doses of adjunctive antidepressant drugs seem to have potential for yielding greater clinical improvement without increasing any risk of manic switch compared to lower doses, at least in carefully selected patients. THE CLINICALTRIALS.NCT00012558.

We conducted a randomised, double-blind, placebo-controlled trial to elucidate the effects of dietary milk fat globule membrane (MFGM) on the physical performance of community-dwelling Japanese adults. For this 24-week study, 115 middle-aged subjects (range 50–70 years old) were invited, of whom 113 (seventy-two women, forty-one men) completed the trial. Participants were then divided into either the placebo control or MFGM group. Measurements of physical performance (without undertaking any mandatory exercise) examining muscle strength, agility and balance were tested every 6 weeks until 24 weeks. Analyses were performed using the intention-to-treat method for all participants. Although the effects of MFGM on muscle strength and agility were not significant, we noted that the parameter for balance (such as the ability to stand on one leg with eyes closed for longer durations) increased in the MFGM group (mean 10·1 (95 % CI 8·25, 12·4) s) compared with the placebo (mean 7·53 (95 % CI 6·11, 9·30) s) (P = 0·046). Similarly, application of the mixed-effect model for repeated measures under unstructured covariance also revealed that the effect of MFGM was significant when compared with the placebo (10·2 (95 % CI 8·33, 12·4) v. 7·61 (95 % CI 6·17, 9·30) s) (P = 0·045). In conclusion, we demonstrated that MFGM had an effect on the physical performance of community-dwelling Japanese adults despite mandatory exercise. However, studies using larger cohorts of individuals from different demographic backgrounds are required to further elucidate the mechanisms underlying these effects and to extend the application of MFGM.

A 31-year-old woman developed a constant cough during the 8th week of pregnancy and was diagnosed with bronchial asthma. She was prescribed prednisolone and inhaled corticosteroids. At 28 weeks of pregnancy, she showed worsening weight loss, fever, night sweats, hoarseness, and coughs. At 31 weeks of pregnancy, a scatter shadow and cavitary lesions were detected on the chest radiograph. Acid- fast bacilli smear test and tuberculosis (TB) polymerase chain reaction tests yielded positive results (G-8), and she was diagnosed with TB. Contact tracing and screening indicated 3 patients with TB onset and 18 patients with latent TB infec- tion attributed to the initial patient, who infected a total of 36 people. In the present case, physicians were reluctant to order a chest radiograph for fear of harming the fetus and did not order sputum or interferon gamma release (IGRA) assay tests either. The diagnosis was delayed by 152 days, which was considered as a factor that caused the outbreak. The diag- nosis of TB in a pregnant patient may be very challenging because symptoms may initially be ascribed to the pregnan- cy, and delayed diagnosis and treatment of military TB can lead to the death of the mother and fetus. Consequently, to ensure early diagnosis and treatment, chest radiography and sputum and IGRA tests are recommended for pregnant women who have TB symptoms or are at high risk for TB.

Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP.A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups.Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients.Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Major Depressive Disorder (MDD) is a major public health concern in that it is associated with increased functional disability and mortality1, 2 as well as a great deal of economic loss.3, 4 MDD is characterized by a variety of symptoms, including depressive mood, diminished interest or pleasure, feelings of worthlessness, and psychomotor agitation; therefore, it is sometimes difficult to thoroughly evaluate their symptoms. Since the appropriate evaluation of symptoms is prerequisite for effective treatment of this illness, recent guidelines recommend the use of systematic rating scales for measurement-based treatment even in daily clinical practice.5-7 There are mainly two types of assessment scales of symptomatology in MDD: clinician-rated and self-rated.8 Although concordance between clinician-rated and self-rated illness severity has been reported to be generally moderate, it is not always perfect.9-12 For example, the presence of personality traits such as low self-esteem and co-morbid borderline personality disorder has been reported to be associated with more severe subjective psychopathology than objectively evaluated by a clinician.13, 14 Moreover, younger age, higher educational background, and female sex are reportedly predictive of higher scores in the self-rated scales relative to the clinician-rated ones.10, 15 Such a gap between clinician-rated and self-rated severity of MDD is not only attributable to flaws in those assessment scales, but to this illness itself, to some extent. For example, this difference could have an impact on the treatment outcomes; patients who regard the illness as more severe than objectively assessed may be more pessimistic about antidepressant treatment, which in turn could result in unfavorable treatment outcomes. To our knowledge, only two studies have tried to address this important issue.16, 17 Rane et al. found that a greater difference between scores in the Beck Depression Inventory (BDI) and the 21-item version of the Hamilton Depression Rating Scale (HDRS21) predicted a slower response to regular routine treatment with pharmacotherapy, psychotherapy, and/or electroconvulsive therapy, independent of objective illness severity, in 103 patients with treatment-resistant depression. On the other hand, they failed to find any significant difference in the difference scores between the subjects who responded and those who did not.16 Dunlop et al. conducted an analysis of data from the Prevention of Recurrent Episodes of Depression With Venlafaxine Extended Release for Two Years (PREVENT) trial, in which participants were divided into the following three groups according to discrepancies between the Inventory of Depressive Symptoms-Self Report score and the 17-item version of the Hamilton Depression Rating Scale (HDRS17) score: concordant patients (n=714), underrating patients (n=164), and overrating patients (n=148). While overrating patients at baseline fulfilled the clinician-rated response criteria more slowly than the others, no significant differences were observed in remission or response rates between the groups.17 However, it is somewhat difficult to extrapolate these findings to a general population with MDD since they solely focused on treatment-resistant or recurrent depression. More critically, the previous studies did not use the same scales for subjective and objective assessments. To address the gap in the literature, in the present study, we examined the association of the difference between subjective and objective severity of the illness with the subsequent response to antidepressant treatment in a greater number of patients with MDD, using the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. In this trial, patients were assessed with both clinician-rated and self-rated scales that include exactly the same items: the 16-item Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C16)18 and the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16).18

This article aims at clarifying the philosophical (=phenomenological) implication of Talcott Parsons’s analytical realism. Generally, his theory is understood as being confrontational to phenomenology; however, in his first book, The Structure of Social Action, Parsons positively referred to Husserl’s Logical Investigations. They shared a sense of crisis: Husserl thought that there was no certain basis in modern science, and Parsons had the feeling that there was no common theory to establish sociology as a science. Thus, both of them criticized the factual sciences of positivism (positivistic empiricism) and showed a strong orientation to the general theory. For this, they depended on conceptual realism (Platonic realism). According to Husserl, scientific knowledge will be arbitrary if the Ideal is not there as the norm of fact. He believed that in truth all people always see Ideas. Similarly, Parsons thought that in truth all people always act toward the Ideal, because the Ideal element is necessarily found through the logical framework of sociology, i.e., the action frame of reference. Hence, he maintained that the Ideal element that gives a normative orientation to actions is real, though analytical, insofar as the social order is established.

We report an outbreak of 64 cases of tuberculosis (TB) that spread in a welfare facility for elderly individuals.First, 64 TB patients who had contact with the source patient were screened at our hospital. We examined the time course up to the discovery of symptoms and analyzed the results for variable numbers of tandem repeats (VNTR) and the drug susceptibility tests. Second, we performed chest computed tomography to examine lesions due to a previous TB infection.The source patient had recurrent aspiration pneumonia. The delay in doctor consultation was considered day 0, and the delay of diagnosis was 267 days. On examining the contacts, we found that 29 patients had TB while 35 had a latent TB infection. Results of the VNTR and the drug susceptibility tests showed that all the patients who developed TB had the same pattern as that of the source patient. Chest computed tomography showed lesions due to a previous TB infection in 8 patients.Based on the results of the VNTR and drug susceptibility tests, we concluded that the outbreak was due to an exogenous infection from the same source. All 8 patients who showed lesions due to a previous TB infection were aged81 years, and TB in these patients was found to be due to exogenous re-infection.

The electrical and thermoelectric characteristics of n-type Mg2Si equipped with electrodes of Ni and the transition-metal silicides CoSi2, CrSi2, TiSi2, and NiSi were examined. To form the electrodes on the Mg2Si matrix, a monobloc sintering method, i.e., simultaneous sintering of the electrode material during Mg2Si sintering, was used. To obtain dense electrodes and to keep an appropriately low sintering temperature for the Mg2Si matrix, a Ni binder was used for the CoSi2, CrSi2, and TiSi2 monobloc sintering. The mixture ratio between the transition-metal silicide and the Ni was 50:50 in wt.%. The room-temperature I–V characteristics of the fabricated CoSi2, CrSi2, and TiSi2 electrodes with the Ni binder and NiSi electrodes were considered to be adequate for practical applications in as much as ohmic contacts were obtained. The contact resistance at the Mg2Si/electrode interface decreased by 35% and 28%, respectively, for the CoSi2 and CrSi2 electrodes compared with our standard Ni electrode. The thermoelectric power output was measured at the practical operating temperature of 600 K, with ΔT = 500 K. The observed output powers for 3.0 mm × 3.0 mm × 7.5 mm samples equipped with CoSi2, CrSi2, and NiSi electrodes were 153 mW, 149 mW, and 125 mW, respectively, representing increases of 27%, 24%, and 4%, respectively, compared with the 120 mW measured for the sample with Ni electrodes.

Fabrication of sintered undoped n-type Mg2Si, initiated from pre-synthesized all-molten polycrystalline Mg2Si powder, was carried out using a Plasma Activated Sintering technique. The thermoelectric properties were evaluated from room temperature up to 861 K. The maximum dimensionless figure of merit was estimated to be 0.60 at 861 K. For output power measurements, the length and cross-sectional area of Mg2Si elements equipped with Ni electrodes were varied from 6 to 15 mm and 2 × 2 to 4 × 4 mm2, respectively. For the 3 × 3 × 7.5 mm3 element, the maximum output power density was 1.43 Wcm-2 with the temperatures of the cool and hot sides being 373 K and 873 K (ΔT = 500 K), while the highest output power was 203 mW for the sample of 4 × 4 × 7.5 mm3 at ΔT = 500 K. The results of aging tests for 11,000 h with the hot side at 873 K and the cool side at 373 K under atmospheric conditions showed that the fabricated device elements possess sufficient durability at high power-generation operating temperatures.

Unlike the case with some other solid tumors, whole genome array screening has not revealed prognostic genetic aberrations in primary gastric cancer. Comparative genomic hybridization (CGH) using bacterial artificial chromosome (BAC) arrays for 56 primary gastric cancers resulted in identification of four prognostic loci in this study: 6q21 (harboring FOXO3A; previously FKHRL1), 9q32 (UGCG), 17q21.1 approximately q21.2 (CASC3), and 17q21.32 (HOXB3 through HOXB9). If any one of these four loci was deleted, the prognosis of the patient was significantly worse (P = 0.0019). This was true even for advanced tumors (stage IIIA, IIB, or IV, n = 39) (P = 0.0113), whereas only 1 of the 17 patients with less advanced tumors (stage IA, IB, or II; n = 17) died of disease after surgery. Multivariate analysis according to the status of four BACs or pathological stage based on the Japanese Classification of Gastric Carcinoma (stages IA, IB, and II vs. stages IIIA, IIIB, and IV) demonstrated that the BAC clone status was also an independent prognostic factor (P = 0.006). These findings may help predict which patients with malignant potential need more intensive therapy, or may point to new therapeutic approaches especially for advanced tumors. The parameter here termed the integrated genomic prognostic biomarker may therefore be of clinical utility as a prognostic biomarker.

More than half of all human cancers are associated with mutations of the TP53 gene. In regard to the functional interaction with the remaining wild-type (WT) p53 allele, p53 mutations are classified into two types, recessive and dominant-negative (DN) mutations. The latter mutant protein has a DN activity over the remaining WT allele. We previously showed that the DN p53 mutant was useful as a predictor of poor outcome or a risk factor for metastatic recurrence in patients with some types of cancers, regardless of the presence or absence of loss of heterozygosity (LOH) of WT p53, suggesting that the DN p53 had 'gain-of-function (GOF)' activity besides the transdominance function. In this study, we investigated GOF activity of two DN p53 mutants which had a point mutation at codon 248 (R248Q and R248W), one of the hot spots, by transfecting them respectively into H1299 cells which originally expressed no p53 protein. Growth activity of the transfectants with the two mutants was not different from that of parent or Mock transfectants. Meanwhile, in vitro invasions of Matrigel and type I collagen gel by R248Q-transfectants were significantly higher than those by R248W-transfectants or the control cells. However, there were no differences in cell motile activities, expressions of extracellular matrix-degradative enzymes such as matrix metalloproteinases, urokinase-type plasminogen activator and heparanase, and their inhibitors, between R248Q- and R248W-transfectants. These findings indicate that the p53 mutants have a different quality in GOF activities even if the mutations occurred at the same codon. And detailed information of the status of p53, including transdominancy and GOF activity, is expected to be useful for diagnosis and therapeutic strategy fitting the individual patients.

We hypothesize that dysregulated expression levels of the developmental regulatory genes in the adult body result in tumor development and malignant progression. PAX genes discovered as human orthologous genes of Drosophila 'paired' encode transcription factors, which control the expression of target genes to go on along the program of development. In this study, we first quantified expression of 9 PAX genes in human nevus pigmentosus tissues, melanoma tissues and melanoma cell lines by the real-time reverse transcription-PCR method. As a result, we found that the expression levels of PAX4 and PAX9 were extremely low in melanoma tissues and cell lines compared to nevus pigmentosus tissues. We then established melanoma cells overexpressing PAX4 and examined roles of PAX4 in cell growth. PAX4-overexpression reduced in vitro cell growth of human melanoma C8161 and MeWo cells. BrdU- uptake assay and cell cycle analysis by flow cytometry indicated that the retardation of cell proliferation by PAX4- overexpression was due to decreased DNA synthesis and cell cycle arrest at the G0/G1 phase. Furthermore, treatment of C8161 and MeWo cells with 5-azacytidine, a DNA demethylating agent, induced the expression of PAX4, suggesting that DNA methylation repressed the PAX4 gene expression in human melanoma. These results suggest that PAX4 functions as a potent tumor suppressor.

We examined expression patterns of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in colorectal cancer tissues to assess their prognostic significance.mRNA expressions of 17 MMPs, 4 TIMPs, and RECK were measured in 112 colorectal cancerous tissues, 20 normal mucosa tissues, and 11 metastatic liver lesions by real-time reverse-transcriptional-polymerase chain reaction. The protein level expressions were confirmed with immunohistochemistry.Cancers and normal mucosa displayed highly significant differences (P0.01) in expression of nine genes (MMP-1, -3, -7, -9, -10, -11, -12, -14, and RECK). Primary cancers and metastatic lesions showed highly significant differences (P0.01) in MMP-1, -10, -11, and TIMP-1. MMP-12 expression was higher in the primary tumors that were associated without hepatic metastasis than those with metastasis (P0.01). High expression of MMP-15 was related to longer disease-free survival (generalized Wilcoxon test, P0.0062; Cox hazard model, P0.028, hazard ratio, 0.099).MMP, TIMP, RECK expression patterns may provide an insight into extracellular matrix degrading (which is characteristic of colorectal cancers) and its role in metastasis.

Matrix metalloproteinase 1 (MMP-1) degrades extracellular matrix and thereby promotes tumor invasion and progression. In this study we examined the prognostic significance of tissue expression levels of MMP-1 mRNA in patients with invasive breast carcinoma.We assessed the prognostic value of MMP-1 mRNA expression in tumor tissue specimens from 85 breast carcinoma patients with a median follow-up time of 38 months (range, 2-48 months). MMP-1 mRNA levels were measured by real-time quantitative reverse transcriptase polymerase chain reaction (real time RT-PCR). The results were correlated with various clinicopathological parameters and clinical outcomes.mRNA expression levels of MMP-1 were higher in tumor tissue specimens than in adjacent normal breast tissue specimens from 15 patients (P0.023). MMP-1 mRNA levels showed no significant relationship with either tumor size or axillary node status but correlated inversely with estrogen receptor levels (P0.0043). High MMP-1 mRNA expression as determined by real-time RT-PCR correlated significantly with a high frequency of recurrence and fatal outcome (P0.025 and P0.020). Multivariate analysis using the Cox regression model indicated that high MMP-1 mRNA expression was an independent unfavorable prognostic factor (risk ratio, 6.37; P0.019).We have demonstrated for the first time the high mRNA expression of MMP-1 in patients whose carcinomas lack estrogen receptor expression. Our results suggest that MMP-1 is an important gene implicated in the progression of human breast cancer.

Objective: Epstein-Barr virus (EBV) has been implicated in the genesis of a variety of human cancers. We aimed to confirm the presence and define the role of EBV in bladder cancer. Methods: A total of 39 bladder cancer specimens were analyzed. Ten urinary bladder tissues obtained at autopsy were used as a normal control. EBV-encoded RNA (EBER) was evaluated by in situ hybridization (ISH). Frozen material available from 18 EBER-positive cases was analyzed by using reverse transcription-polymerase chain reaction for BZLF1, an early lytic gene product. The expression of CD20, CD3, ZEBRA (BZLF1 product) and transforming growth factor β1 (TGFβ-1) was assessed using an immunohistochemical technique. Results: Infiltration of EBER-expressing lymphocytes was detected in 26 of 39 bladder cancer cases (66.7%). A small fraction of the tumor cells as well as the infiltrating lymphocytes were positive in two cases. All normal urinary bladder specimens showed negative results. The incidence of EBV-positive lymphocyte infiltration was significantly higher for advanced stage cancers than those in earlier stages (Ta-152% vs T2-4 93%, P = 0.013). The presence of BZLF1 mRNA was demonstrated in seven out of the 18 EBER-positive cases. Conclusions: Infiltration of EBV-harboring lymphocytes occurs in a large subset of bladder cancers cases. It is more frequently associated with advanced stages. EBV infection in tumor cells is very limited. Our findings suggest that EBV-positive lymphocytes might play a role in bladder cancer progression.

Since 2005, Tomakomai National College of Technology has been conducting “A Promotion Program of Academic-Industrial Collaboration with Active and Joint Participation by Technical College Students” , in which the students actively challenged to resolve technical problems of local companies through internships and graduation researches. This project was adopted as part of the Support Program for Contemporary Educational Needs by the Ministry of Education, Culture, Sports, Science and Technology. It has been revealed that the program is practical and effective engineering education for the students, i.e. “Future Engineers” . In addition, it leads to the revitalization of local companies which carried out collaborative researches with the participating students.

It has been reported that an endogenous matrix metalloproteinase (MMP) inhibitor, reversion-inducing cysteine-rich protein with Kazal motifs (RECK), is able to inhibit tumour angiogenesis, invasion, and metastasis through inhibition of MMP-2, MMP-9, and membrane type-1 (MT1)-MMP (MMP-14) secretion and activity. In this study, using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR), we have analysed RECK expression levels in resected non-small-cell lung cancer (NSCLC) tissue and compared these data with the clinicopathological features of these patients to investigate the role of RECK in NSCLC. We have also analysed the expression of MMP-2, MMP-9, and MMP-14 and compared the data with those for RECK expression. Tissue samples of primary lung cancers were obtained from a total of 83 patients [46 with adenocarcinomas (ADC) and 37 with squamous cell carcinomas (SCC)] who underwent curative resection. The samples were taken from 83 tumours and 20 matched normal lung tissue samples as controls. Expressions of RECK in ADC and SCC were significantly lower than in the control. In ADC tissue, the expression of RECK was higher in stage IA than in stage IB-IIIA. There was no such a correlation in SCC. In ADC, univariate analysis for relapse-free survival using Cox regression analysis identified low RECK expression (p=0.036), low MMP-14 expression (p=0.038), and tumour T2 (p=0.034) as significant negative prognostic predictors. However, in SCC, none of the clinicopathological factors assessed, including RECK expression, had prognostic value. In conclusion, our study suggests that suppression of RECK expression is involved in the progression of ADC of the lung and that RECK expression in resected ADC of the lung is a favorable predictor of patients' prognosis.

Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ-specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p

HOX genes encode transcription factors that play a key role in morphogenesis and cell differentiation during embryogenesis of animals. Human neuroblastoma cells are known to be chemically induced to differentiate into neuronal or Schwannian cells. In the present study, we investigated the roles of HOX genes in differentiation of GOTO neuroblastoma cells into Schwannian cells. When GOTO cells were grown in the presence of 5-bromo-2'-deoxyuridine (BrdU), they increased the expressions of two HOX genes (HOXC6 and HOXC11) and marker genes for Schwannian cells (S100beta and myelin basic protein). Forced expression of HOXC11 alone or both HOXC6 isoform 1 and HOXC11 induced the expression of S100beta in GOTO cells. In transient transfection experiments, the overexpression of HOXC6 and HOXC11 transactivated the S100beta promoter-reporter construct. Taken together, our results suggest that HOXC6 and HOXC11 are associated with differentiation of GOTO cells into Schwannian cells through the transcriptional activation of S100beta gene.

Dry gas cleaning was performed using five different commercial activated carbons (ACs) at 150-300°C. Phenol, o-cresol, naphthalene, and 1-methylnaphthalene were employed as the tar model compounds that produced from biomass gasification. The effect of the adsorption temperature and physical characteristics of ACs on the adsorption behaviors such as the breakthrough curves and adsorption capacities was investigated using a fixed-bed reactor. At 150°C, o-cresol and naphthalene were effectively removed; the adsorption capacities of the ACs were 13.4-19.4g-tar/(100g-AC) and 19.9-23.7g-tar/(100g-AC) in o-cresol and naphthalene, respectively. For effective tar removal, a larger surface area, a smaller average particle size, and an appropriate pore diameter were necessary. The effect of the tar model compounds on the adsorption behavior was investigated using the same AC at 150°C. The adsorption capacity was found to be 10.5-32.6g-tar/(100g-AC) in the following order : phenol

Psychophysiological markers have been focused to investigate the psychopathology of psychiatric disorders and personality subtypes. In order to understand neurobiological mechanisms underlying these conditions, fear-conditioning model has been widely used. However, simple aversive stimuli are too simplistic to understand mechanisms because most patients with psychiatric disorders are affected by social stressors. The objective of this study was to test the feasibility of a newly-designed conditioning experiment using a stimulus to cause interpersonal conflicts and examine associations between personality traits and response to that stimulus. Twenty-nine healthy individuals underwent the fear conditioning and extinction experiments in response to three types of stimuli: a simple aversive sound, disgusting pictures, and pictures of an actors’ face with unpleasant verbal messages that were designed to cause interpersonal conflicts. Conditioned response was quantified by the skin conductance response (SCR). Correlations between the SCR changes, and personality traits measured by the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised NEO Personality Inventory were explored. The interpersonal conflict stimulus resulted in successful conditioning, which was subsequently extinguished, in a similar manner as the other two stimuli. Moreover, a greater degree of conditioned response to the interpersonal conflict stimulus correlated with a higher ZAN-BPD total score. Fear conditioning and extinction can be successfully achieved, using interpersonal conflicts as a stimulus. Given that conditioned fear caused by the interpersonal conflicts is likely associated with borderline personality traits, this paradigm could contribute to further understanding of underlying mechanisms of interpersonal fear implicated in borderline personality disorder.

We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin beta3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin beta3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays. The integrin beta3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin alphav subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectantsthe integrin beta3-transfectantsthe control transfectants or parental cells. E-cadherin was expressed in the integrin beta3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin beta3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin alphav beta3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.

Aim: To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation. Methods: Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts. Results: Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein–Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients’ tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts. Conclusions: SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.

Adsorption and catalytic decomposition of H 2 S and COS were investigated over active carbons using a flow reactor with fixed bed in the temperature range from 300 to 450 °C. Active carbons removed very effectively COS at a relatively high temperature of 400 °C, some portion being decomposed to CO over active carbons. Although H 2 S was also removed by active carbons at 400 °C, the removal capacity of H 2 S was much smaller than that of COS and H 2 S was hardly decomposed over active carbons. The impregnation of Fe on the active carbon enhanced very much the removal of both COS and H 2 S; however, their decomposition behaviors were much different. It is found that the decomposition of H 2 S was enhanced by Fe-supported activated carbon derived from a brown coal, while no decomposition of COS took place over the same Fe-supported active carbon. These results indicate that H 2 S may be dominantly removed through the reaction with metal to produce metal sulfide, while COS may be preferably adsorbed as COS itself in the pore of active carbon and then may react with carbon surface to be decomposed to CO. Such contrast adsorption and decomposition behaviors of COS and H 2 S are discussed based on their chemical reactivity over active carbon-supported catalyst.

Background: Although cancer cells appear to maintain the machinery for intrinsic apoptosis, defects in the pathway develop during malignant transformation, preventing apoptosis from occurring. How to specifically induce apoptosis in cancer cells remains unclear. Methods: We determined the apoptosome activity and p53 status of normal human cells and of lung, colon, stomach, brain, and breast cancer cells by measuring cytochrome c-dependent caspase activation and by DNA sequencing, respectively, and we used COMPARE analysis to identify apoptosome-specific agonists. We compared cell death, cytochrome c release, and caspase activation in NCI-H23 (lung cancer), HCT-15 (colon cancer), and SF268 (brain cancer) cells treated with Triacsin c, an inhibitor of acyl-CoA synthetase (ACS), or with vehicle. The cells were mock, transiently, or stably transfected with genes for Triacsin c-resistant ACSL5, dominant negative caspase-9, or apoptotic protease activating factor-1 knockdown. We measured ACS activity and levels of cardiolipin, a mitochondrial phospholipid, in mock and ACSL5-transduced SF268 cells. Nude mice carrying NCI-H23 xenograft tumors (n = 10) were treated with Triacsin c or vehicle, and xenograft tumor growth was assessed. Groups were compared using two-sided Student t tests. Results: Of 21 p53-defective tumor cell lines analyzed, 17 had higher apoptosome activity than did normal cells. Triacsin c selectively induced apoptosome-mediated death in tumor cells (caspase activity of Triacsin c-treated versus untreated SF268 cells; means = 1020% and 100%, respectively; difference = 920%, 95% CI = 900% to 940%; P

Accurate preoperative prediction of lymph node metastasis and degree of tumor invasion would facilitate an appropriate decision of the extent of surgical resection of cancers to reduce unnecessary complication or to minimize the risk of recurrence in patients. We analyzed gene expression profiles characteristic of the invasiveness of colorectal carcinoma in a total of 89 cases, using a cDNA array and pattern classification algorithms. We set binary classes for a panel of clinicopathologic parameters, each of which was divided at different levels for categories (discrete) or values (continuous). We searched an optimal combination of genes to discriminate the classes by using of a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, Por = 0.05). We used a sequential forward feature selection which additively searched a combination of genes, giving a minimal leave-one-out classification error rate of a k-nearest neighbor classifier. In the process of gene preselection, we found a remarkable difference in the expression pattern of genes according to the anatomical location of cancers. The difference was most prominent when the classes were set for cecum, ascending colon, transverse colon, and descending colon (CATD) versus sigmoid colon and rectum (SR). By stratifying these two locations, we were able to extract gene expression profiles characteristic of the classes of the presence versus absence of lymph node metastasis, lymphatic invasion, vascular invasion and degree of mural invasion, and pathological stages, with an accuracy of more than 90%. These results suggest that colorectal cancers harbor distinct molecular pathophysiological statuses according to their right-to-left locations, of which stratification is important for pattern classification of cDNA array data.

Background We assessed the predictability of various classes of gastric carcinoma defined by clinicopathological parameters, such as invasiveness and clinical outcomes, using cDNA array data obtained from 54 cases. Materials and methods We searched an optimal combination of genes to discriminate the classes defined with the clinicopathological parameters by using a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P ≤ 0.05). With the selected features (gene set), we evaluated the predictability of each parameter in a leave-one-out cross-validation test. Results We successfully selected sets of genes for which the classifier predicted better versus worse overall survival (tumor-specific death) and tumor-free survival (recurrence), with respective classification rates of 94 and 92%. A contingency table analysis (χ 2 test) and Cox proportional hazard model analysis revealed that lymph node metastasis is the most important factor (confounding factor) in patients’ prognoses and risks of recurrence. The feature subset selection procedure successfully extracted expression patterns characteristic of lymph node metastasis and lymphatic vessel invasion, yielding 92 and 98% prediction accuracies for these respective factors. Conclusion We conclude that expression profiling using feature subset selection provides a powerful means of stratification of gastric cancer patients in regard to the prognostic factors. Further studies should be warranted to apply this method to personalization of the treatment options.

The aim of this paper is to consider how ‘Now and So’ can be now and so. The theory of social systems as a second order observer observes the phase ‘Now and So’ in system time of a first order observer because it is always a blind spot for the first order observer.For this purpose, (1) I will formulate the theory of social systems by Niklas Luhmann as “Sociological Phenomenology”: Parallel to consciousnesses, social systems are observed not as things but as subjects in the world. However, (2) contrary to phenomenological sociology, I start not from ‘the problem of meaning is a problem of time’ but from ‘the problem of time is a problem of meaning’. This means that system time is a meaningful construction. Finally, (3) I show that the phase ‘Now and So’ can be now and so through the distinction of past/future. In whole system time, an event as an element of the system can appear and disappear in the present.