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Die Prinzipientheorie Robert Alexys erhebt Anspruch darauf, die bei Grundrechtsfragen vom Bundesverfassungsgericht vorgenommene Verhältnismäßigkeitsprüfung zu erklären. Dieser Beitrag untersucht, ob diese Behauptung tatsächlich stimmt, und kommt vor allem zum Schluss, dass die „Gewichtsformel“, die sich Alexy für die Verfeinerung der Abwägungsmethode beruft, den Entscheidungen des Gerichts nicht entspricht. In der Abwägung selbst versucht er die Kompetenz des demokratischen Gesetzgebers in Betracht zu ziehen und erkennt deswegen das „formelle Prinzip“ an, das rechtfertige, in die „Gewichtsformel“ die „epistemische Variable“ einzuziehen. Danach könne der Gesetzgeber auch mit nicht sicheren Einschätzungen etwa über die Intensität der Verletzung der betroffenen Interessen Beschränkungen der Grundrechte begründen. Jedoch geht die Prüfung des Bundesverfassungsgerichts immer davon aus, dass der Gesetzgeber angeblich mit Sicherheit die Verfassungsmäßigkeit der Grundrechte beschränkenden Gesetze begründet hat. Das ist die Voraussetzung der Verschiedenheit seiner Kontrollintensität, die nicht bedeutet, dass die Erkenntnisse des Gesetzgebers unsicher sein dürfen. Dieser Beitrag findet den theoretischen Hintergrund dieser Diskrepanz darin, dass die Gefahr selbst als Grund der Beschränkung der Grundrechte gilt, was Alexy in seiner „Gewichtsformel“ nicht korrekt darstellen kann.

Objectives This study aimed to observe the life prognosis of persons with dementia during the first five years after registering for long-term care insurance, and to determine the factors affecting their prognosis.Methods A total of 556 persons, aged 65 years or older newly registered for long-term care insurance in a city in Japan, were observed. The life prognosis of the registered persons was determined using standardized mortality ratio (SMR) with the general population as a standard, and relevant factors were observed in terms of dependence indices of dementia and disability.Results The mean age of persons newly registered for long-term care insurance was 81.6 years and 63% of them were females. Mortality during the first 4.5 years after registration was 16.7% p.a., with males and those of older age having higher rates. The SMR was 1.80 for all individuals, with males and those of younger age having a higher SMR. The SMR increased with the severity of the disability (higher classes on the disability dependence index) at the time of the registration, while no significant trend was seen in SMR with the dementia dependence index. Multivariate analysis revealed that mortality was dependent on sex (malefemale), age (olderyounger), disability dependence indices (higher classeslower classes), and current place of residence (homefacility), while there were no significant trends found in mortality with degree of severity on the dementia dependence indices. The adjusted odds ratios of dying from respective factors were as follow: from sex (male/female, with male as a standard) 0.35 (95% confidence interval 0.24-0.51), from age group (65-74 years/75-84/85+, stepwise with 65-74 years as a standard) 1.84 (1.39-2.47), from disability dependence index (normal/I/Ⅱa/Ⅱb..., stepwise with "normal" as standard) 1.38 (1.21-1.58), and from place of residence (home/facility, with home as a standard) 0.64 (0.42-0.99). When limited to only the elderly with dementia dependence indices of Ⅱa-Ⅳ, the analysis showed similar results.Conclusion Elderly persons registered for long-term care insurance had higher mortality rates than the general population that was dependent on the disability dependence index, but not on the dementia dependent index. Further studies are therefore necessary to elucidate the factors relevant to the study's finding.

[Objectives and Materials] Based on the tuber- culosis (TB) surveillance database, the incidence rates of TB infection and active disease among healthcare workers were observed for female nurses and male doctors in 2010 in comparison with those of the general population. [Results] The relative risk (RR) of active TB among female nurses aged 20-69 years was 4.86 (95% confidence interval: 4.31-5.45) for 2010, which has increased from 2.30 observed in 1987-1997. The RR was highest for nurses aged 20-29 years at 8.84 and declined with age until 3.60 for those aged 50-59 years that was still significantly higher than 1. For male doctors the RR was significantly higher than 1 only for those aged 39 years or younger. The rates of those who were -indicated for treatment of latent TB infection (LTBI) were clearly higher among healthcare workers; for female nurses the RR was 32.7 (95% CI: 30.5-35.0), ranging from the highest level of 62.8 among those aged 20-29 years down to 11.6 for those aged 60-69 years. For male doctors also, the RR was high at 9.7 (7.9- 11.7) for 20-69 years, ranging from 14.5 for those aged 20- 29 years down to 5.3 for those aged 60-69 years. [Discussion] TB cases of nurses and doctors were more likely to be detected by the active case finding measures such as periodic screening and contact investigations than cases in the general population, which indicates the current effort of addressing the occupational exposure in the healthcare set- tings. The high level of risk of TB disease as Iwell as LTBI among healthcare professions and its possibly increasing trend as. seen in female nurses warrants further strengthening of monitoring of the problem and overall countermeasures in their workplaces.

The procedure of ultra-rapid extraction (PURE) and loop-mediated isothermal amplification for tuberculosis (LAMP-TB) is a simple and rapid manual tuberculosis diagnostic with medium-throughput capability. Because of its simplicity, this method could be useful in resource-limited conditions such as microscopy centers in developing countries. This study was conducted to evaluate the clinical performance of this method in a point-of-care setting. The performance was compared to that of smear microscopy and liquid culture in a hospital laboratory in Haiti, which is considered a representative facility for the implementation of this method. The sensitivity, based on culture-positivity, was 86% (95% confidence interval: 81.3-90.3%) and that based on the smear-negative and culture-positive results was 51% (38.7-63.5%). The specificity based on sample negativity for both smear and culture was 98.4% (96.8-99.2). These results are nearly equivalent to those of a clinical study performed in Japan and are comparable with those of other nucleic acid amplification methods. Thus, approximately 18% more tuberculosis patients could be identified by adding the LAMP-TB method to routine smear microscopy in field settings in Haiti. In addition, it is suggested that local technicians could perform LAMP-TB after only short-term training.

The non-positivist Robert Alexy recognizes that the legal positivism is principally correct from the observer’s perspective. The legal positivist Hans Kelsen takes this perspective. They agree on this point. Their minds separate, however, when they are asked about the meaning of the participant’s perspective for the legal science. While Kelsen denies it clearly, Alexy takes the participant’s perspective to be necessary for the recognition of law, because the claim to correctness which law always lays can be understood only with this perspective. Kelsen tries to grasp the normativity of law with the famous “basic norm”, but he admits at the same time that one need not necessarily presuppose it. Horst Dreier realizes that Kelsen’s basic norm implies that the validity of law is dependent on the “existentialistic” decisions of individuals. With this in mind, Kelsen’s legal theory draws closer to the participant’s perspective of Alexy. I do not think, however, that Dreier correctly explains the role of the basic norm in the legal science. I resort to Joseph Raz, who introduces “a hypothetical point of view” for the scientific observation of law. Then we face the last question: if the legal science may be satisfied with such a hypothetical perspective or it needs the participant’s perspective, as Alexy claims. He claims so because he recognizes the moral value of the positive law. Kelsen does not think so, therefore he cannot tolerate the legal science participating in the legal practice. I find Alexy more persuasive. The legal system of modern states is worth supporting. His directly moral legitimation of law should be corrected, however. I explain this point with the help of the legal philosophy of Jurgen Habermas .

Background: During the latter half of the 19th century, Japan experienced a historical epidemic of TB along with the progress of the industrial revolution that accompanied modernization and urbanization. Adolescent women recruited for textile factories were the main victims. After 1910, the epidemic seemed to subside and mortality took a downward, although very slow, course. However, this new trend was soon interrupted as Japan entered the Sino-Japanese War in 1931 followed by World War II in 1941. Summary: During the war period from 1931 through 1945, the massive mobilization of young males to battle was accompanied by new trends of economy centering on the heavy industry that also mobilized young males to urban factories. TB mortality again began to rise after 1931 until it reached 241 per 100,000 (estimated) in 1944, causing a serious excess of TB deaths over the baseline trends since 1910. This rate is the second highest in Japan's TB history. The main victims were young male soldiers and factory workers. The total number of excess TB deaths during this 15-year period is estimated to be 490,000, i.e., 22% more than the expected number of TB deaths during this period. This excess mortality diminished soon after the end of the war, and the mortality rate returned to the level expected by extrapolation over the basic trend line that had started around 1910. Key Notes: Governmental and non-governmental organizations made tremendous efforts in public health and clinical services during the war period. These efforts bore fruit only after the end of the war, bringing about the very fast decline of TB mortality exceeding 10% per year. Of course, this improvement was greatly supported by the advent of modern chemotherapy and other preventive measures such as BCG vaccination and X-ray screening that became widely available after the war.

Objectives To elucidate the changes in cognitive function in elderly individuals as observed in the results of a long-term care certification survey.Methods The data were obtained from the long-term care insurance of 121 subjects who applied for benefit renewal between 2010 and 2011, in a city in Japan. The subjects were grouped into one of three groups (improved, maintained, or worsened) according to the change in status of overall cognitive function. Analyses were completed with this grouping as the main dependent variable and with sex, age, degree of independence at the initial insurance application in 2006, and levels of seven categories of cognitive function as independent variables.Results There was a statistically significant association between age and deterioration of various cognitive functions. Sex had no significant effect on the rate of deterioration. The initial degree of independence was positively associated with the cognitive function change. Multivariate analysis (logistic regression analysis) incorporating age, sex, and initial degree of dependence as independent variables revealed that sex does not significantly influence the prognosis of cognitive function. Changes in the score of each of the seven cognitive functions were analyzed with ANOVA, with categories of functions and individuals as sources of variance. Both function category and individuals were significantly associated with deterioration. Among the seven categories of functions, "understanding daily activities" had the greatest deterioration, while "calling him/herself by his/her own name" had the least.Conclusion Cognitive function, as observed in the long-term care certification survey, is more likely to deteriorate in elderly individuals and in those who were at higher levels of dependency index at the time of initial certification, and this effect is observed equally in men and women. Our results suggest that, in providing long-term care for elderly people, it may be useful to call the clients by their names and ask them to name themselves, as well as to try to improve their understanding regarding the daily activities by articulating the components of each activity.

At the dawn of the twentieth century, tuberculosis (TB) was Japan’s most serious health problem. General improvement in living conditions led to a steady decline in the TB epidemic, with reappearances during the influenza pandemic and wartime episodes. The Japan Anti-Tuberculosis Association was founded in 1939. The BCG vaccine was widely administered by the late 1940s, and the introduction of streptomycin further reduced TB mortality. The first nationwide TB prevalence survey was conducted in 1953. Surveys were conducted at 5-year intervals until 1973, when they were replaced by the TB registry. The registration services were first computerized in 1987. Results are thoroughly analyzed and published as monthly summaries and annual reports. Today, Japan’s TB burden remains intermediate. The most formidable challenge in TB control comes from the aged population. Efforts to manage the elderly, socioeconomically marginalized, and the isolated will be critical in lowering the incidence of TB and preventing resurgence.

Electrical engineering staff (reorganized to Electrical and Computer engineering in 2004) has taught electrical engineering students for mathematics classes in Wakayama National College of Technology (WNCT) in Japan from 2007. Effects of the mathematics classes by the electrical engineering staff were evaluated by using the results of the mathematics placement tests. The results of the tests are compared with averages of other National Colleges of Technology in Japan and other divisions of WNCT. As a result, an ability of electrical engineering students for mathematics improved dramatically with increasing the ratio of mathematics classes by the electrical engineering staff. It should seem that these good results were achieved by eagerness and strong motivation of the staff with electrical specialty for improving the ability of their division's students. The reasons for the improvement are discussed and the unique class of mathematics for college of technology is also introduced.

Diagnosis and treatment of tuberculosis (TB) will likely navigate a historical turning point in the 2010s with a new management paradigm emerging. However, global control of TB remains a formidable challenge for the decades to come. The estimated case detection rate of TB globally was 66%, and there were 310 000 estimated multidrug-resistant TB (MDR-TB) cases among the 6.2 million TB patients notified in 2011. Although new tools are being introduced for the diagnosis of MDR-TB, there are operational and cost issues related to their use that require urgent attention, so that the poor and vulnerable can benefit. World Health Organization (WHO) estimated that globally, 3.7% of new cases and 20% of previously treated cases have MDR-TB. However, the scale-up of programmatic management of drug-resistant TB is slow, with only 60 000 MDR-TB cases notified to WHO in 2011. The overall proportion of treatment success of MDR-TB notified globally in 2009 was 48%, far below the global target of 75% success rate. Although new tools and drugs have the potential to significantly improve both case detection and treatment outcome, adequate health systems and human resources are needed for rapid uptake and proper implementation to have the impact required to eliminate TB. Hence, the global TB community should broaden its scope, seek intersectoral collaboration and advocate for cost reduction of new tools, while ensuring that the basics of TB control are implemented to reduce the TB burden through the current ‘prevention through case management’ paradigm.

Performance of interferon-γ (IFN-γ) release assays still needs to be improved. The data on the performance of QuantiFERON-TB Gold Plus (QFT-Plus), a new-generation of QFT assay are limited. This study evaluated the diagnostic performance of QFT-Plus, and compared to that of QuantiFERON-TB Gold In-Tube (QFT-GIT). Blood samples were collected from 162 bacteriologically confirmed tuberculosis (TB) patients and 212 Mycobacterium tuberculosis-uninfected volunteers; these samples were then tested with QFT-GIT and QFT-Plus. The IFN-γ concentration of QFT-Plus was lower than that of QFT-GIT in TB patients (p

The 90 years since the foundation of the Japanese Society for Tuberculosis in 1923 can be divided into three periods by three turning points, i.e., epidemiological transitions: 1911-1950 (the first period), 1953-1980 (the second period) and 1980-present (the third period). The progress of the Society is overviewed for each of these periods, and the several specific areas of research and control efforts are discussed. The first period might be viewed as a preparatory phase during which various tremendous efforts were made in basic, clinical, and epidemiological research that would bear fruit during the second period. Following this period, modern technologies were introduced into the national tuberculosis control program accompanied by related basic research, including the development and evolution of the theory of TB pathogenesis, X-ray diagnosis, and clinical trials of chemotherapy, of which the Society has been very proud. The problems of activities in the second period were carried over into the third period, together with the epidemiological challenge of the slowing of epidemiological improvement. For this period, the bibliometric technique was applied in the trial of objectively analyzing the trends of research, activities in publication. In addition, the USA's efforts to maintain awareness of TB, after the unexpected upsurge of TB during 1980s-90s due to its neglect in the past, were cited as lessons Japan should now learn.

PURPOSE The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. METHODS The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. RESULTS Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj. OR 48.17 CI 29.62-79.75 in Group 4; and OR 4.24 CI 2.86-6.31, adj. OR 15.61 CI 9.05-27.26 in Group 5. The univariate analysis and multivariate regression analysis revealed an influence of the BCG immunization delivery manner on the BCG immunization coverage. CONCLUSION The choice of BCG immunization delivery manner is very important to raise the BCG immunization coverage. The BCG immunization given on the occasion of the mass health check-up and the high-frequent immunization service are thought to improve the BCG immunization coverage.

The reported effect of anti-tuberculosis chemotherapy on interferon-gamma (IFN-γ) release in response to specific Mycobacterium tuberculosis antigens has been inconsistent. The objective of this study was therefore to determine the effect of anti-tuberculosis chemotherapy on IFN-γ response to ESAT-6 and CFP-10. QuantiFERON®-TB Gold (QFT-G) was performed, and the IFN-γ response to ESAT-6 and CFP-10 were measured, for 50 people with culture-confirmed tuberculosis prior to initiating treatment and periodically for up to 120 weeks following initiation of said treatment. IFN-γ responses and bacteriological response were compared. The average IFN-γ response to ESAT-6 and CFP-10 and the proportion of QFT-G results that were positive decreased during chemotherapy and for several weeks thereafter, reaching lows at weeks 48 to 56. Furthermore, these measures were lower at 48 weeks for those with bacteriological reversion prior to the second monthly visit than for those with slower reversion. Although it was shown that anti-tuberculosis treatment generally reduced the specific release of IFN-γ, the effect is so variable that it could be used as a monitor of progress of chemotherapy with great care and reservation.

Isoniazid (INH) is a key agent in the treatment of tuberculosis. In Mycobacterium tuberculosis, INH is converted to its active form by KatG, a catalase-peroxidase, and attacks InhA, which is essential for the synthesis of mycolic acids. We sequenced furA-katG and fabG1-inhA in 108 INH-resistant (INH(r) ) and 51 INH-susceptible (INH(s) ) isolates, and found three mutations in the furA-katG intergenic region (Int(g-7a) , Int(a-10c) and Int(g-12a) ) in four of 108 INH(r) isolates (4%), and the furA(c41t) mutation with an amino acid substitution in 18 INH(r) isolates (17%). These mutations were not found in any of 51 INH(s) isolates tested. We reconstructed these mutations in isogenic strains to determine whether they conferred INH resistance. We found that the Int(g-7a) , Int(a-10c) and Int(g-12a) single mutations in the furA-katG intergenic region decreased katG expression and conferred INH resistance. In contrast, the furA(c41t) mutation was not sufficient to confer INH resistance. These results suggested that downregulation of katG is a mechanism of INH resistance in M. tuberculosis and that mutations in the furA-katG intergenic region play a role in this resistance mechanism.

The aim of this study was to establish the importance of detecting fluoroquinolone (FQ) resistance in multidrug resistant (MDR) Mycobacterium tuberculosis, and to show the usefulness of a hybridization-based line probe assay (LiPA) for detecting gyrA mutations. Thirty-three MDR M. tuberculosis isolates were collected from a total of sixty MDR isolates identified in Japan over 6 months during a national surveillance study in 2002. Seventeen MDR isolates were collected by the National Center for Global Health and Medicine in Japan over 6 years from 2003 to 2008. These 50 isolates were examined for FQ susceptibility, and analysed by LiPA and gyrA sequencing. Among them, 22 (44 %) showed FQ resistance. All FQ-resistant isolates had at least one mutation in gyrA. The results of the LiPA were fully consistent with the DNA sequencing results. Given that on the basis of our results almost half of the MDR M. tuberculosis isolates in Japan might have resistance to FQ, it is important to monitor FQ resistance in patients with MDR tuberculosis (TB), as well as with drug-susceptible TB, prior to commencing treatment. For the detection of FQ resistance, LiPA is useful and can rapidly and efficiently assess FQ resistance.

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis , and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis 'DOTS' model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A(1c) (HbA(1c)) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.

The histogenesis of folliculosebaceous cystic hamartoma (FSCH), including the origin of the frequently associated adipocytes and other mesenchymal components, remains unclear. There are controversial problems regarding FSCH, such as the relationship between FSCH and trichofolliculoma (TF), and the exact concept of sebaceous TF. Fourteen FSCHs and 1 sebaceous TF were revaluated for the histopathology and studied for immunohistochemical profile of various cytokeratins, hair follicular stem cell markers, and others. The nestin expression was partly upregulated in the sebaceous duct structures and the proliferating spindle cells in the surrounding connective tissue in some lesions. S-100 protein staining clarified the presence of lipogenesis in these nestin-expressed lesions, and the nestin-positive spindle cells were also seen around the immature adipocytes. Some FSCHs showed the focal follicular differentiation, where no signs of catagen or telogen stage were seen. One peculiar case showed both FSCH and TF features equally. The possibility that the adipocytes and other mesenchymal components in FSCHs originated from the nestin-positive multipotent stem cells was suggested. It is not convincing that FSCH and TF represent a chronological change in the spectrum of the same condition. Each FSCH and TF is therefore considered to be a distinctive entity. They may develop under a similar pathogenesis differing from each other in the direction of fundamental differentiation. In contrast to the TF lesions, the unusual upregulation of nestin expression is occasionally seen in FSCH lesions, including their stromas, which may thus result in the production of various kinds of mesenchymal components in FSCHs.

Background Both trichoblastoma and basal cell carcinoma (BCC) are considered to be a benign and malignant neoplasm of follicular germinative cells respectively. A recent investigation revealed that the mesenchymal cells in the perifollicular sheath and evolving follicular papilla of embryonic hair germs and those cells in hair follicles in early anagen express nestin. Objective The aim of the present study was to investigate whether trichoblastoma and BCC recapitulate the epithelial–mesenchymal interactions in embryonic hair germs or early anagen hair follicles by expressing nestin in stromal cells. Methods Immunohistochemical staining was performed with antibody against nestin for 15 trichoblastomas including large/small nodular, retiform and trichoepithelioma types, while adding the superficial type associated with nevus sebaceous and for 20 BCCs including superficial, nodular, nodulo-infiltrative, and infiltrative/micronodular types. Results In all 15 trichoblastomas, the stromal cells expressed nestin with variable positive reactions, except for superficial trichoblastomas within nevus sebaceous lesions, in which stromal cells were constantly positive for nestin. In all 20 BCCs, the stromal cells were basically negative for nestin. Conclusions The development of trichoblastomas incompletely recapitulates the epithelial–mesenchymal interactions in embryonic hair germs or early anagen hair follicles, whereas BCCs fundamentally have lost this ability. Among the various types of trichoblastomas, the superficial type associated with nevus sebaceous was found to have the most similar character to either embryonic hair germs or early anagen hair follicles.

Few investigations on the histopathology of trichofolliculoma (TF) have so far included an immunohistochemical study. To seek new insight into TF with a revaluation of the histopathological features and an investigation of the immunohistochemical profile, 14 TFs were revaluated for the histopathology and the immunohistochemical profile of various cytokeratins (CKs), hair follicle stem cell markers, and others. The CK15 expression was upregulated in the basal cells from the primary cystic structures beyond to secondary follicles without expression of CK19. CK16 and CK17 were positive in the suprabasal cells of the primary cystic structures and the immature secondary hair follicles. No exact isthmus/bulge region was seen in the anagen secondary hair follicles, and newly developed (tertiary) hair follicles arose randomly from the involuting secondary follicles. Ber EP4 expression was generally weakened in the secondary or tertiary hair germ-like structures. The size of secondary hair follicles varied from vellus hair follicles to terminal hair follicles, even though no lesions located on the regions where the terminal hairs develop were included in this study. S-100 protein-positive wavy spindle cells were accidentally found in the surrounding connective tissue of the secondary follicles in 2 TF lesions. TFs were characterized by the proliferation of abnormal CK15-positive hair follicle stem cells, which basically differentiated toward the outer root sheath and attempting to make hair but losing the proper differentiation. The control of the size of the anagen hair follicles and the regular hair cycle were also disordered.

The Asia–Pacific region accounts for about 20% of the global burden of tuberculosis (TB). However, there are a wide variety of TB problems between countries and areas. This variety could be described in three dimensions: (i) historical trends of the TB epidemics, closely related to the advent of industrialization or urbanization; (ii) success in modern TB control in the early days; and (iii) expansion of the directly observed therapy, short course (DOTS) strategy during the past 20 years. Moreover, these dimensions have been subject to the ‘health infrastructure’ based on such social goods as people's education, economic standards, and social security or stability. The Asia–Pacific Region offers very good examples to illustrate the roles of these factors in leading to such a variety of TB problems as seen today. Thus, this region was the first to achieve the global target of DOTS by the end of 2005, that is to detect 70% of patients and to treat them with DOTS, and to successfully cure 85% of those detected. However, we should remember that we are currently challenged by TB combined with HIV infection and AIDS; TB with drug-resistance, especially multidrug-resistant (MDR) or extensively drug resistant (XDR) forms; TB in people with special risk factors, for example diabetes and senility; and other medical and socioeconomic problems. At the same time, we have to be careful about the premature loss of people's interest in TB, due to illusion or unfounded optimism, especially among medical professionals and the government.

Making a differential diagnosis to distinguish dermatofibrosarcoma protuberans (DFSP) from dermatofibroma (DF) is occasionally difficult. In those instances, CD34 and factor XIIIa have been used as valuable differential markers. The histogenesis of DFSP, however, remains uncertain and controversial, although it is generally thought to be a neuromesenchymal neoplasm. Nestin is an intermediate filament protein that was first observed in neuroectodermal stem cells. We investigated the expression of nestin in order to distinguish between DFSP and DF in combination with the use of conventional markers, CD34 and factor XIIIa. The nestin expression was investigated in tissue specimens from 16 DFSP cases and 30 DF cases. The expression of other differential markers such as CD34, factor XIIIa, CD163 and CD10 was also observed in these samples. Fifteen (94%) of 16 cases of DFSP showed the expression of nestin, whereas only four (13%) of 30 cases of DF showed the expression of nestin. Most of the DFSP cases showed a diffuse positive reaction in more than half of the tumor cells. In contrast, DF cases with nestin expression showed a partial positive reaction. Nestin is considered to be a useful and additional marker in combination with CD34, factor XIIIa and CD163 in order to distinguish between DFSP and DF. The frequent expression of nestin in DFSP may therefore indicate that DFSP is derived from putative, multipotent neuromesenchymal cells.

Dieser Beitrag handelt von der Entstehung und Entwicklung des Begriffs „Schmahkritik“ in den Entscheidungen zum Verhaltnis von Meinungsfreiheit und Ehrenschutz. Der Schwerpunkt liegt in der geschichtlichen Betrachtung der wechselseitigen Einflusse von BVerfG und BGH. Der Beitrag mundet in einer kritischen Beurteilung der heutigen Rechtslage. Im Luth-Urteil erklarte das BVerfG die grundsatzliche Vermutung fur die freie Rede uber offentliche Angelegenheiten. Der BGH reagierte darauf mit der Einfuhrung der Rechtsfigur „Schmahkritik“, die als mit Diffamierungsabsicht geubte, deswegen ausnahmsweise nicht geschutzte Kritik definiert wurde. Bis in die 1980er Jahre machte sich das BVerfG allerdings diesen Begriff nicht zu Eigen. Es legte Wert auf die Vorbeugung gegen die generalpraventive, „einschuchternde Wirkung“ auf Auserungswillige. In den 1990er Jahren fuhrte es doch die „Schmahkritik“ in seine eigene Dogmatik ein. Gerade das verursachte aber die damalige heftige Kritik am BVerfG, weil es aus seiner...

The apathy of bystanders often prevails when instances of bullying, hidden crime and extortion occur in communities such as schools, business work areas, underclass ghettos, prisons and the military. The present study models apathetic behavior as a non-cooperative game and attempts to verify this theory through experiments. Furthermore, our research suggests that the apathy of bystanders generally decrease as the number of citizens in a community decrease. In our experimental cases, if the number of members in a group decreases from 40 members to 20 members, the concerned and helpful behavior of bystanders increases by 21%.

BACKGROUND: To develop a more accurate methodology for diagnosing active tuberculous pleurisy, as well as peritonitis and pericardits of tuberculous origin, we established an antigen-specific interferon gamma (IFN-gamma)-based assay that uses cavity fluid specimens. METHODS: Over a 19-month period, 155 consecutive, nonselected patients with any cavity effusion were evaluated. Study subjects were 28 patients with bacteriologically confirmed active tuberculous serositis and 47 patients with definitive nontuberculous etiology. Culture was performed for 18 h with fluid mononuclear cells in the supernatant of the effusion together with saline or Mycobacterium tuberculosis-specific antigenic peptides, early secretory antigenic target 6 and culture filtrate protein 10. IFN-gamma concentrations in the culture supernatants were measured. RESULTS: In patients with active tuberculous serositis, antigen-specific IFN-gamma responses of cavity fluid samples were significantly higher than those of nontuberculous effusion samples. Area under the receiver operating characteristic (AUROC) curve was significantly greater for cavity fluid IFN-gamma response (AUROC curve, 0.996) than for cavity fluid adenosine deaminase and whole-blood IFN-gamma responses (AUROC curve, 0.882 and 0.719, respectively; P = .037 and P < .001, respectively). Although the AUROC curve was greater for cavity fluid IFN-gamma response than for background cavity fluid IFN-gamma level (AUROC curve, 0.975), the AUROC curves were not statistically significantly different (P = .74). However, multivariate logistic regression analysis revealed that cavity fluid IFN-gamma responses were significantly associated with the diagnosis, even after adjustment for background IFN-gamma level (adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42; P < .001). CONCLUSIONS: The cavity fluid IFN-gamma assay could be a method for accurately and promptly diagnosing active tuberculous serositis.

Resistance of Mycobacterium tuberculosis to pyrazinamide (PZA) derives mainly from mutations in the pncA gene. We developed a reverse hybridization-based line probe assay with oligonucleotide probes designed to detect mutations in pncA . The detection of PZA resistance was evaluated in 258 clinical isolates of M. tuberculosis . The sensitivity and specificity of PZA resistance obtained by this new assay were both 100%, consistent with the results of conventional PZA susceptibility testing. This assay can be used with sputa from tuberculosis patients. It appears to be reliable and widely applicable and, given its simplicity and rapid performance, will be a valuable tool for diagnostic use.

We developed a DNA sequencing-based method to detect mutations in the genome of drug-resistant Mycobacterium tuberculosis . Drug resistance in M. tuberculosis is caused by mutations in restricted regions of the genome. Eight genome regions associated with drug resistance, including rpoB for rifampin (RIF), katG and the mabA ( fabG1 )- inhA promoter for isoniazid (INH), embB for ethambutol (EMB), pncA for pyrazinamide (PZA), rpsL and rrs for streptomycin (STR), and gyrA for levofloxacin, were amplified simultaneously by PCR, and the DNA sequences were determined. It took 6.5 h to complete all procedures. Among the 138 clinical isolates tested, 55 were resistant to at least one drug. Thirty-four of 38 INH-resistant isolates (89.5%), 28 of 28 RIF-resistant isolates (100%), 15 of 18 EMB-resistant isolates (83.3%), 18 of 30 STR-resistant isolates (60%), and 17 of 17 PZA-resistant isolates (100%) had mutations related to specific drug resistance. Eighteen of these mutations had not been reported previously. These novel mutations include one in rpoB , eight in katG , one in the mabA-inhA regulatory region, two in embB , five in pncA , and one in rrs. Escherichia coli isolates expressing individually five of the eight katG mutations showed loss of catalase and INH oxidation activities, and isolates carrying any of the five pncA mutations showed no pyrazinamidase activity, indicating that these mutations are associated with INH and PZA resistance, respectively. Our sequencing-based method was also useful for testing sputa from tuberculosis patients and for screening of mutations in Mycobacterium bovis . In conclusion, our new method is useful for rapid detection of multiple-drug-resistant M. tuberculosis and for identifying novel mutations in drug-resistant M. tuberculosis .

Novel lophine dimer (hexaarylbiimidazole, HABI) containing a hydrophilic oligo-ethylene glycol group was prepared as a radical initiator. Absorption of a lophyl radical generated by photo dissociation of the lophine dimer was observed around 600nm by photo irradiation at 254nm. Electron beam (EB) pulse radiolysis of the lophine dimer suggested generation of lophyl radical by EB irradiation similarly, showing that the material is also applicable to electron beam lithography. The lophine dimmer showed excellent stability in developing solution and high resolution due to introduction of hydrophilic substituent.

Background and objective: QuantiFERON®-TB Gold (QFT-G) was employed in a contact investigation in a high school to evaluate its performance in adolescents. Methods: Students of the same school grade as the index case were screened with tuberculin skin test (TST) and CXR examination as an initial contact investigation. QFT-G was performed for students demonstrating a positive TST (erythema larger than 30 mm). Results: Of 349 students whose TST was completed, 95 had positive TST responses, although the distribution of TST responses was similar for both high and low exposure groups. In contrast, only four of the 88 TST-positive students tested with QFT-G were positive by this test, and three of these were from the high exposure group. Chemoprophylaxis was provided to only those four QFT-G-positive students. Follow up of the 91 students who were TST-positive, but QFT-G-negative (or not tested), for more than 3.5 years revealed that none have developed active tuberculosis. Conclusions: QFT-G appears more specific than TST as contacts with positive TST and negative QFT-G responses were not offered prophylaxis and none developed tuberculosis during 3.5 years of follow up. The replacement of TST with QFT-G, or perhaps combined use of TST and QFT-G, may be more useful in diagnosing true infection and thus reducing the number of subjects indicated for chemoprophylaxis.

We, group of tuberculosis experts, made discussions over how to improve the quality of treatment of multidrug resistant tuberculosis using a newly developed anti-tuberculosis drug, and at the same time, how to prevent the disadvantages of the treated patients and also that of persons who would be infected with newly produced drug-resistant bacilli, by preventing the emergence of resistance to the new drug. A series of proposals are made.

Mn-doped Pb(Zr,Ti)O3 (PMZT) thin film have been successfully crystallized in a sol–gel process at 440 °C, at which temperature polyimide film does not decompose. With a 6.8 V DC applied bias (272 kV/cm) in the effective capacitance area, capacitance density is 20 nF/mm2, and leakage current density is 0.2 µA/cm2. With a continuously applied 6.8 V DC bias, 0.2 mol % Mn-ion doping results in an increase from 4.0 to 12.5 years in the time to dielectric breakdown, as extrapolated to 85 °C, without degrading capacitance. Mn-doped Pb(Zr,Ti)O3 (PZT) thin-film capacitors on polymer film appear to offer capacitance and reliability that are both high enough for use as decoupling capacitors.