PubMed Health⌕ Search

Biomedical subjects

Hitoshi Tsuda

Publications and source records attributed to Hitoshi Tsuda.

At least 55 records · Page 3Linked to original sources

Utility of axillary ultrasound examination to select breast cancer patients suited for optimal sentinel node biopsy.

BACKGROUND: Because sentinel node (SN) biopsy (SNB) is known to produce false-negative results, we examined the usefulness of axillary ultrasound (AUS) in selecting patients suitable for optimal SNB. METHODS: A positive AUS finding (positive AUS) was defined as an echo pattern of a homogeneously hypoechoic SN without an echo-rich center, indicating massive to extensive nodal involvement. The identification of SNs was performed, and complete axillary dissection was carried out. RESULTS: A total of 262 women were enrolled into the study (T1 disease = 94; T2 disease = 145; and T3 disease = 23). The incidence of positive AUS increased with increasing size of breast tumor (P <0.0001). The overall identification and false-negative rates were 88.2% and 10.8%, respectively. However, when limited to AUS-negative patients, SNs were identified in 205 of 208 patients (98.6%), and the false-negative rate was 1.7%. CONCLUSIONS: AUS should be included in the preoperative procedure for the selection of breast cancer patients suitable for SNB.

Axilla↗

Reproducible immunohistochemical criteria based on multiple raters' judgments for expression of thymidine phosphorylase in breast cancer tissue.

In order to accurately determine the expression of thymidine phosphorylase (TP) in breast cancer, it is important to develop an appropriate system for immunohistochemical staining evaluation. Three raters, pathologists A-C, independently judged the status of TP in both cancer cells and cancer stromal tissue in 586 breast cancers immunohistochemically. TP expression levels were categorized into four groups (scores 0-3), and scores of 2 and 3 were considered as positive. Interrater and intrarater agreement levels in the judgment of TP expression were analyzed by the kappa statistics. By combining three raters' judgments, we sought for the optimal evaluation system that generates the best concordance among all judgments. The numbers of TP-positive cases were 294 (50.2%), 309 (52.1%) and 344 (58.7%) for cancer cells and were 315 (53.8%), 383 (65.4%) and 397 (67.7%) for cancer stromal tissue in the judgments by pathologists A, B, and C, respectively. There was no correlation of TP immunostaining between cancer cells and cancer stroma tissue. Interrater agreement levels were substantial for cancer cells (kappa = 0.652) and moderate for cancer stroma tissue (kappa = 0.438). Intrarater agreement level for TP judgment by pathologists A, B, or C was substantial to almost perfect for cancer cells (kappa = 0.755-0.880), and for cancer stromal tissue (kappa = 0.620-0.752). The level of TP expression estimated under the majority system and the total scoring system setting a cut-off score between 4 and 5 revealed the highest concordance with the three raters' judgments. To accurately evaluate the TP status in breast cancer tissue, three or more raters are needed and the majority system and total scoring system appear appropriate.

Breast Neoplasms↗

The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma.

OBJECTIVES: Recent studies have shown that some growth factor receptors with tyrosine kinase activity, eg, the epidermal growth factor receptor (EGFr) and the c-erbB-2 (HER-2) oncoprotein, are associated with aggressive biologic behavior of various cancer cell types. We examined the clinicopathological significance of the expression and localization of EGFr and HER-2 in both invasive and intraductal components of ductal adenocarcinomas of the pancreas. METHODS: Tissue samples from 76 archival cases of pancreatic ductal adenocarcinoma were immunohistochemically analyzed for both membrane and cytoplasmic overexpression of EGFr and HER-2 oncoprotein. The rate of incidence between the invasive and intraductal components was analyzed and then their correlation with tumor differentiation and patient prognosis was analyzed. RESULTS: Cytoplasmic EGFr overexpression was more frequent in invasive components (47 of 76, 62%) than in intraductal components (19 of 76, 25%), while membrane EGFr overexpression was more frequent in intraductal components (41 of 76, 54%) than in invasive components (11 of 76, 14%). The membrane HER-2 overexpression was also more frequent in intraductal components (15 of 76, 20%) than in invasive components (2 of 76, 3%), but the incidence of cytoplasmic HER-2 overexpression did not differ between intraductal components (12 of 76, 16%) and invasive components (8 of 76, 11%). The cytoplasmic EGFr overexpression in invasive components was more frequent in grade 3 group (32 of 33, 97%) than in grade 2 (15 of 32, 47%) and grade 1 groups (0 of 10, 0%) (P < 0.001). Patients with adenocarcinoma with cytoplasmic EGFr overexpression showed shorter overall survival than those with adenocarcinoma without cytoplasmic EGFr overexpression (P = 0.02). CONCLUSION: It is suggested that the cytoplasmic overexpression of EGFr plays a significant role in the progression of pancreatic ductal adenocarcinoma, especially in the invasion and acquisition of aggressive clinical behavior. Both membrane and cytoplasmic expression of HER-2 showed no significant correlation between tumor differentiation and poor survival.

Aged↗

Difference in cytoplasmic localization pattern of neutral mucin among lobular endocervical glandular hyperplasia, adenoma malignum, and common adenocarcinoma of the uterine cervix.

To investigate whether the cytoplasmic localization pattern of neutral mucin differs between lobular endocervical glandular hyperplasia (LEGH) and cervical adenocarcinoma (CxAd), including minimal-deviation adenocarcinoma (MDA), or adenoma malignum, alcian blue (pH 2.5)/periodic acid-Schiff (AB-PAS) staining was performed to formalin-fixed paraffin-embedded tissue sections of 13 lesions of LEGH and 53 tumors of CxAd, including 6 tumors of MDA. The cytoplasmic localization of neutral mucin was classified as a "whole cytoplasmic pattern," in which neutral mucin filled the cytoplasm entirely, or as an "apical pattern," in which neutral mucin was localized in the subsurface area only. Cytoplasmic neutral mucin patterns were detected in all 13 cases of LEGH and in 19 cases (36%) of CxAd, including five cases of MDA. The localization of neutral mucin was always the whole cytoplasmic pattern in 13 cases of LEGH, but was the apical pattern in these 19 cases of CxAd. The other 34 cases of CxAd, including 1 case of MDA, corresponded to the acid mucin pattern stained purple or blue or no staining pattern by AB-PAS. Among the 53 cases of CxAd, the apical neutral mucin pattern was an indicator of poorer patient prognosis by univariate and multivariate analyses. The examination of cytoplasmic localization of neutral mucin might be applicable, not only to differential diagnosis between LEGH and CxAd, including MDA, but also to estimate clinical aggressiveness of CxAd.

Adenocarcinoma↗

Clinicopathologic and technical factors associated with the uptake of radiocolloid by sentinel nodes in patients with breast cancer.

PURPOSE: Sentinel-node biopsy is becoming widely accepted in breast cancer treatment. Using the radioisotope technique, a lower risk of identification failure is related to the amount of radiocolloid in the sentinel nodes. The aim of this study was to identify the factors associated with the colloidal uptake of the sentinel nodes. METHODS: Technetium-labeled colloid was injected peritumorally, with or without subdermal injection. According to the maximum radioactivity of the sentinel nodes, patients were divided into high (>/=100 counts/s) or low (<100 counts/s) uptake groups. The uptake was compared in relation to the clinicopathologic and technical features. RESULTS: The sentinel node was identified in 183 of 186 patients (98.4%), with 60 and 123 patients in the low- and high-uptake groups (mean: 39 and 1003 counts/s), respectively. Multivariate analysis showed that an age of 65 years or older and a sentinel-node size of 8 mm or more were significantly more predominant in the low-uptake group. CONCLUSION: Care must be taken when performing sentinel-node biopsy, especially for aged patients and for those with large sentinel nodes. The optimal technique should be determined on the basis of these results.

Adult↗

Interobserver variation in the diagnosis of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix.

To examine the interobserver agreement level of the histological diagnosis of adenoma malignum (ADM), 52 proliferative endocervical glandular lesions were evaluated independently by four observers (A to D), each of whom is in charge of gynecological pathology at a different hospital. The correlation of diagnosis by each observer with patient outcome was also examined for 19 of these lesions. When the diagnoses were categorized into benign lesions including hyperplasias, ADM, and common types of adenocarcinoma, consistent diagnoses among all observers were achieved for only 12 lesions (23%), with a slight level of interobserver agreement (kappa=0.115). The points of disagreement were as follows: (i) whether proliferative endocervical glandular lesions preserving lobular structures were diagnosed as benign or as ADM; and (ii) whether proliferative endocervical glandular lesions with a discrete area of obvious adenocarcinoma were diagnosed as ADM or as common-type adenocarcinoma. The mortality rates of patients with ADM diagnosed by observers A, B, C, and D were 60% (3 of 5), 25% (3 of 12), 14% (1 of 7), and 13% (2 of 15), respectively. Therefore, ADM diagnosed by observers A and B was frequently lethal, whereas ADM diagnosed by observers C and D was mostly non-lethal and might contain benign lesions. The diagnosis of ADM covered various spectra of proliferative endocervical glandular lesions among the observers. Disagreement in the diagnosis was suggested to derive largely from the absence of consensus criteria for differential diagnosis among benign hyperplastic lesions, ADM, and common adenocarcinoma, and from differences in the observers' interpretations about cellular atypia and invasion.

Adenocarcinoma↗

Primary carcinoid tumor of the testis: Immunohistochemical, ultrastructural and FISH analysis with review of the literature.

Primary carcinoid tumor of the testis only accounts for 0.2% of all carcinoid tumors in Japan. The clinicopathological features, including differences between Japanese and Europe/United States (Eur/US) series', which are known in ovarian carcinoids, have not yet been sufficiently recognized. In the present study, five testicular carcinoids from various clinicopathological viewpoints were analyzed, with a review of the literature. All 15 cases in Japan, including 10 previously reported, were insular carcinoids. Three of the 15 cases (20%) were associated with a teratoma. Serotonin production was confirmed in at least 10 cases (five cases in the present study and five cases in previous studies), but carcinoid syndrome was present in only two cases. Three of the 15 cases (20%) showed distant metastases, and the tumors that metastasized were larger than those that did not. These features were almost similar to those observed in the Eur/US series. Three pure carcinoids were also studied for the number of sex chromosomes by fluorescence in situ hybridization (FISH). They did not show a significant numerical abnormality of the X chromosome, which is common in testicular germ cell tumors. Therefore, the genetic background of pure carcinoids might be different from that of common germ cell tumors.

Adult↗

Interlaboratory comparison in HercepTest assessment of HER2 protein status in invasive breast carcinoma fixed with various formalin-based fixatives.

Although formalin-based fixatives are used in pathologic laboratories, there is no strictly standardized fixation protocol in Japan. To examine interlaboratory variation caused by different conditions of fixation in the assessment of human epidermal growth factor receptor (HER) 2 status on pathologic tissues, 274 archival invasive breast carcinomas from 5 different laboratories were evaluated using the HercepTest. In 1 laboratory in which 10% neutral buffered formalin was used, as recommended by the manufacturer, the overexpression rate was 22.4% and fell within the statistical expected range (20%-30%) for HER2 overexpression in breast carcinomas. The overexpression rates in the other 4 laboratories, in which either 20% nonbuffered formalin or 15% neutral buffered formalin was used, were near the expected range for HER2 overexpression. To clarify the influence of prolonged formalin fixation on the HercepTest, we compared 1-day with 7-day fixations using 36 cases fixed with 20% nonbuffered formalin. Of the 36 cases, 7 showed 3+ staining with 1-day fixation and sustained the same scoring results with 7-day fixation, although the staining intensities in these cases were reduced with the prolonged fixation. These results indicated that the immunohistochemical assessment of HER2 status with the HercepTest was comparatively resistant to prolonged fixation conditions and provided stable staining results in positive cases, particularly 3+ patients.

Antibodies, Monoclonal↗

Different expression patterns of KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins between epithelial and mesenchymal components in uterine carcinosarcoma.

Uterine carcinosarcoma histologically comprises the components of epithelial and mesenchymal malignancies, and is known to be clinically highly aggressive. To reveal the significance of the expression of tyrosine-kinase-receptor-type oncoproteins in this tumor type, the incidence and distribution of the KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins were immunohistochemically examined in 16 surgically resected cases. For 6 cases, the EGFR and HER-2 amplifications were also examined by fluorescence in situ hybridization (FISH). In the epithelial component, overexpressions of KIT, EGFR, and HER-2 were detected in 4 (25%), 5 (31%), and 9 (56%) cases, respectively, whereas these overexpressions in the mesenchymal component were detected in 6 (38%), 8 (50%), and 1 (6%) cases, respectively. KIT and EGFR were co-overexpressed in the mesenchymal component of 4 cases and in the epithelial component of 2 cases. However, HER-2 overexpression was mostly detected in the epithelial component only, and tended to occur independently of KIT and/or EGFR overexpression. By FISH, one of the 4 cases with HER-2 overexpression showed low-level gene amplification. In two cases with EGFR overexpression, the gain of EGFR alleles and/or polyploidization of chromosome 7 had occurred. The expression patterns of KIT, EGFR, and HER-2 differed between the epithelial and mesenchymal components, and the regulation of their expression appeared important in the acquisition of mesenchymal metaplasia in uterine carcinosarcoma. Structural and/or numerical alterations of chromosomes might be in part involved in EGFR and/or HER-2 overexpression in this tumor type.

Carcinosarcoma↗

Reduced expression of GNA11 and silencing of MCT1 in human breast cancers.

Alteration in the methylation status of a gene is often associated with its altered expression. Based on a genome scanning technique for differences in CpG methylations, methylation-sensitive representational difference analysis, DNA fragments hypermethylated in a human breast cancer were isolated. A DNA fragment was isolated from intron 1 of guanine-nucleotide-binding protein alpha-11 (GNA11). mRNA expression of GNA11 was shown to be decreased in 10 of 16 breast cancers by RT-PCR analysis, and the immunoreactivity of the GNA11 product, Galpha11 subunit of heterotrimeric G-protein, was observed to be reduced in 14 of the 16 cancers by immunohistochemistry. Methylation of a CpG island (CGI) in the 5' region of GNA11 or that of intron 1 did not show a clear correlation with its decreased expression. Another DNA fragment was isolated from a CGI in the 5' upstream region of monocarboxylate transporter 1 (MCT1), and was methylated in 4 of 20 breast cancers. The CGI was also methylated in a human breast cancer cell line, MDA-MB-231, and quantitative RT-PCR showed that its expression was almost lost in the cell line. By treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine, the methylation was removed and the expression was restored. GNA11 is involved in signalling of gonadotropin-releasing hormone receptor, which negatively regulates cell growth. MCT1 is involved in cellular transportation of butyrate, which induces cellular differentiation. Downregulation of these two genes was suggested to be involved in human breast cancers.

Biological Transport, Active↗

[Cyclothymia and typus melancholicus: empirical study on personality character of mood disorder].

PURPOSE: 1. To investigate whether depressive, cyclothymic, hyperthymic and irritable temperaments as identified by TEMPS-A are characteristic to monopolar or bipolar disorder. 2. To investigate the independency and to discuss the clinical validity of the temperaments. 3. To replicate the previous studies whether Typus Melancholicus is characteristic to monopolar disorder. 4. To investigate the relationship between Typus Melancholicus and mood dysregulation, and the relationship, if any, is characteristically observed with monopolar disorder. 5. To discuss the difference between monopolar and bipolar disorder in terms of personality character. SAMPLE: Monopolar and bipolar groups were recruited consecutively from the patients who received outpatient treatment at Kanto Medical Center between September and November, 2001. The age is between 18 and 60. The exclusion criteria were psychotic disorder, organic disorder, grave physical illness and non-remitted mood symptoms (HRSD > 11 and MRS > 13). Control group was selected from 1391 company employees who participated in TEMPS-A research project between May 2001 and May 2002, matching gender and age with monopolar and bipolar groups. The exclusion criterion was marked depressive symptom (CES-D > 16). STATISTICAL ANALYSIS: The statistical analyses were done with Kruskal-Wallis test and Mann-Whitney U test with Bonferroni's correction regarding the difference among the groups. Spearman coefficients were examined regarding the independency of temperaments. The relationship between Typus Melancholicus and mood dysregulation was examined by mono-regression analysis. RESULT AND DISCUSSION: Depressive and cyclothymic temperaments scores did not differ significantly between monopolar and bipolar. These scores were significantly higher in monopolar and bipolar than in control. Therefore, these temperaments are evidenced to be characteristic with mood disorder. But between monopolar and bipolar there was no significant difference. Irritable temperament score did not differ significantly among the three groups. This score showed a highly significant correlation with cyclothymic and depressive temperaments. Irritable temperament seems closely related with the personality character of mood disorder, however this temperament itself was not characteristic. Hyperthymic temperament score was mildly significantly lower in bipolar than in control. There was no other significant inter-group difference. This temperament hardly showed a correlation with other temperaments. Though hyperthymic temperament may be hypothesized characteristic with manic patients, the result did not support this hypothesis. Typus Melancholicus score did not differ significantly among three groups. This result contradicts with a number of previous studies. It seems that the prevalence of Typus Melancholicus among the groups should be further investigated. Typus Melancholicus showed a mild correlation with depressive temperament in monopolar and with depressive, cyclothymic and irritable and temperaments in bipolar. Regarding mono-regression analysis, no temperament predicted Typus Melancholicus formation in monopolar. Depressive, cyclothymic and irritable temperaments predicted significantly in bipolar. In control group, hyperthymic temperament predicted midly significantly, but the prediction rate was as small as 7%. These results seem to support the theories of Shimoda and Matussek that Typus Melancholicus characters are related with bipolar disorder. Between monopolar and bipolar, there was not much significant difference in terms of personality characteristics. This seems to suggest no marked personality character difference between these groups and supports Akiskal's concept of Bipolar Spectrum. CONCLUSION: 1. Depressive and Cyclothymic temperaments are characteristic with mood disorder. 2. Hyperthymic temperament is independent, but not characteristic with mood disorder. 3. Irritable temperament may be modifying the personality character of mood disorder. 4. Typus Melancholicus was not characteristic to monopolar disorder. 5. Significant relationship between Typus Melancholicus and mood dysregulation was observed in bipolar group. 6. There seems no substantial difference between monopolar and bipolar disorders in terms of personality character.

Adolescent↗

["Shuuchaku" in various types of manic-depressive patients].

Shimoda's concept of "statothymia" consists of the hypothesis on the characteristic of the emotionality of manic-depressive patients (Shuuchaku-temperament) and the typological description of their personality (Shuuchaku-personality). According to him their emotion, when it has once arisen in relation to something, hardly diminishes. This characteristic constitutes a neurophysiological basis of the disease. The persons, who have this characteristic of emotionality, are quite reliable persons in society, who make every effort to accomplish their obligation, to take responsibility. But at the same time under the overloading situation they are not able to get out of the persistent involvement in work and consequently fall into depressive or manic phases. Although this concept is even today relevant to the core group of mood disorder, it has also some limitations. There are lots of cases in which overwork does not precipitate the manifestation of the disease. The loss of an important person and the change in surroundings are classically well known precipitating situations of melancholic phases. Nowadays such cases are also found, in which failure to acquire a desirable social environment or a romantic partner precipitates the outbreak of the disease. Furthermore such patients of younger generation categorized into "soft bipolar spectrum" defined by Akiskal are far from socially reliable persons, rather maladjusted. Shuuchaku-personality or Typus melancholicus, which is almost equivalent of it, constitutes only one of the various types of patients, together with such types as manic type, avoidant-dependent type and "soft bipolar" type. This article aims at, not only by following Shimoda's concept but also by taking the ordinary meaning of the Japanese word "Shuuchaku" into consideration, presenting a new formulation applicable to various types of the patients of mood disorder. The Japanese word "Shuuchaku" orginally means "sticking to" or "preoccupied with" a certain object, surrounding, or ideal. We consider that in manic-depressive patients the self, which has once been strongly connected with such objects or ideals hardly retreats into past and sticks to the present self. This formulation is not only in accordance with Shimoda's hypothesis on the characteristic of emotionality but also it reveals how the problem of object relation and that of temporality are interconnected with each other in manic depressive patients. One of the prominent features of the melancholic symptoms is that patients have the feeling of irrevocability. This indicates in return that in their premelancholic phase they live rather in revocable time. This revocable time is, from our view, the time in which the past self does not completely retreat and always sticks to the present self. In the patients of Typus melancholicus, since the self, which has well been settled in a stable surrounding, always sticks to the present self, the present self continues to avoid an irrevocable change. At the same time since the self, which has not completely taken responsibility, sticks to the present self and drives it to achieve more preciseness in taking responsibility, the order of their surrounding is maintained before it is irrevocably disintegrated. However overloading and unexpected changes in their surrounding could undermine their revocable time and lead them to the outbreak of the disease. In contrast the patients of manic type are not able to settle down in a stable surrounding, rather they often develop conflict with it. In them the self, which could have acquired a desirable condition but has not, sticks to the present self and drives it to seek more ideal conditions outside of the surrounding already given to them. In them the failure to acquire a new desirable condition could precipitate the disease. Furthermore their life course could be close to that of "soft bipolar" patients, when it becomes unstable through the conflict and the disillusion with their surrounding and the consequent withdrawal from real social life.

Bipolar Disorder↗

[Structuralistic and meta-psychological approaches to ambivalence in schizophrenia].

The word "ambivalence" generally signifies a psychic state in which a subject holds a contradictory or conflicted attitude towards an object. The literal meaning of the word is that two valences occur simultaneously, and this connotes the epistemological and ethical problem of where and how the valences arise. The concept of ambivalence implies that the relationship between the subject and the world is ambivalent, that the subject has free will in the alternative evaluation, and that the meanings of the two valences derive from the meta-level outside the world. These reflections lead us to the supposition that ambivalence is closely associated with the function of language. The ambivalent attitude of the subject divides the significance of the object; the appearance of the given ambivalent meanings is the moment of the subject's choice. This phenomenon of division, choice, and given meanings is more than analogous to F. de Saussure's conception of language in terms of sign, différenciation, and l'arbitraire de langue. A view of ambivalence as a fundamental phenomenon concerning subject, world, and language affords insight specifically into ambivalence in schizophrenia. For people with schizophrenia, ambivalent conflict often takes the form of a dichotomy between "good and bad". The more severe the ambivalent symptom, the more similar it seems to a philosophical question about the nature of existence in the world. When schizophrenic people raise philosophical questions directly such as "Is my existence good or bad?" or "To be or not to be?", they seek approval for their existence, assaying to live with "good" intentions. Unfortunately they come to be blamed for harbouring "bad" intentions. When they have an interrogative attitude even to everyday matters, they cannot resolve such questions as "Is the red cup good or bad?", or "Is the green cup good or bad?", and hence "Which cup should I use?". If the projection of the self into the world is essentially the choice of a daily behavior as its own praxis, such indecisiveness thus entails existential conflict. The alternatives of choice appear before them as a tollgate to the world. Wishing admission to the world, they choose the thing that they think "good", but which later turns out to be "bad". These consequences sometimes occur in their inner conflicts and sometimes in their paranoidhallucinatory experiences. We have observed that in these processes, there is an inversion between "good and bad", and "bad" predominates, driving patients to despair. Rethinking E. Bleuler's conception of the ambivalence of schizophrenia, we have found that it is accessible to structuralistic and meta-psychological interpretations. From the viewpoint of linguistic semiology, ambivalence can be considered as a disorder of exclusive differentiation in the associative system resulting from the appearance of antithetical meanings, a phenomenon that is also common in primal words and children's thinking. In the context of psycho-analysis, it is suggested that the dominance of the negative side in ambivalence may be caused by death instinct. These interpretations are consistent with both the philosophical considerations and the clinical observations introduced above, but the problem of schizophrenic specificity is still opened beside the affinity between philosophical conflict and schizophrenic ambivalence. References to ethical and philosophical thinking shed light on the sources of the dichotomous existential conflict and the characteristic inversion between "good and bad" that schizophrenic patients experience. Descriptions of the root of ambivalence can be traced back to ancient times. In the Ecclesiastes of the Apocrypha, Jesus, son of Sirach, elucidates the fundamental ambivalence of will, teaching that the subject has the power of its own choice: at its most extreme, the choice between life and death. In the modern age, L. Wittgenstein offers a strict description of this ambivalence in his "Notebooks 1914-1916". Wittgenstein doubted the possibility of pure subjectivity without individual will and furthermore argued that the will is either good or evil, that is, the bearer of good and evil. In his view, good and evil are somehow connected with the meaning of the world, and meaning ("Sinn" in German) is discerned from significance ("Bedeutung" in German). He went on to write that the meaning does not lie in the world but outside it. As K. Shingu has noted, Wittgenstein's conception is essentially consistent with psycho-analysis. The subject recognizes the world with ambivalent will, the world appears with ambivalent significance, but its ambivalent meaning is given from outside the world, that is, from the meta-level. For E. Husserl's concept of intentionality, it is said that the fundamental disorder of schizophrenia is a preverbal or pre-predicative problem that is connected with intentionality. Yet one wonders whether or not pure, neutral intentionality is really possible. Presumably, intentionality has an intrinsic ambivalence, since the fundamental relationship between the subject and the world may itself be ambivalent. When one becomes conscious of a thing, the potential exists to divide one's intentionality between "good and bad", and the thing thus appears as "good" or "bad". In the healthy psyche, this intrinsic ambivalence emerges only in ethical or philosophical thinking. In schizophrenia, however, the ambivalence of intentionality is explicitly engaged in diverse situations. The inversion of "good and bad" observed in the clinical context signifies that the will of the patient shifts from "good" to "bad", alluding to a contradiction between the subject and the world that is logically inevitable due to the structure of their relationship. The subject objectivfies the world positively, yet is contained by the world passively. That the subject simultaneously announces and is announced in the language system also reflects this paradoxical relationship. Thus, ambivalence of dichotomy between "good and bad" is the very basic phenomenon of consciousness, and the inversion of "good and bad" is a reflection of the structure of the relationship of the subject and the world. If the schizophrenic specificity exists, it may involve the exposure of this intrinsic ambivalence and this paradoxical structure in confrontations with the tellgate into the world under the dominance of the negative side.

Humans↗

Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy.

Inhibition of, or increased resistance to, apoptosis is a common property of cancer cells. This means that a constitutive activation of antiapoptotic molecules via genetic or epigenetic mechanisms, including gene amplification, may well be involved in carcinogenesis. Recently we reported that cIAP1, an inhibitor of apoptosis, is overexpressed through 11q22 amplification in cell lines derived from esophageal squamous cell carcinomas and is associated with resistance of esophageal squamous cell carcinomas to drug-induced apoptosis (I. Imoto et al. Cancer Res., 61: 6629-6634, 2001). Because amplification of 11q22 has been implicated in other malignancies also, including cervical squamous cell carcinomas (CSCCs), we attempted to correlate amplification and overexpression of cIAP1 with radiation sensitivity in CSCC-derived cell lines and primary CSCC tumors. In the nine cell lines we examined, two showed amplification and consistent overexpression of cIAP1, as well as significant resistance to radiation-induced cell death as compared with lines showing no cIAP1 amplification. Immunohistochemical analysis of 70 primary CSCCs from patients treated only with radiotherapy demonstrated that both overall survival and local recurrence-free survival was significantly poorer among patients with tumors showing high levels of nuclear cIAP1 staining than among patients whose tumors revealed little or no nuclear cIAP1. Multivariate analysis showed nuclear cIAP1 staining to be an independent predictive factor for local recurrence-free survival after radiotherapy among patients with CSCC. These findings demonstrate that cIAP1 may play an important role in the development/progression of this disease and that cIAP1 could be a novel predictive marker for resistance to radiotherapy in individual CSCC patients.

Adult↗

Different pattern of loss of heterozygosity among endocervical-type adenocarcinoma, endometrioid-type adenocarcinoma and adenoma malignum of the uterine cervix.

It is unclear which chromosome arms frequently show loss of heterozygosity (LOH) in adenocarcinoma of the uterine cervix. To identify such chromosomal arms, LOH on 52 different chromosome loci was examined using laser capture microdissection and PCR-LOH analysis in 25 common-type adenocarcinomas, comprising 13 cases of endocervical type, 12 cases of endometrioid type and 7 cases of adenoma malignum without the component of conventional endocervical-type adenocarcinoma (designated as "pure" form). In adenocarcinomas of endocervical type and endometrioid type, LOH was commonly detected on chromosome arms 17p (62% and 50%, respectively), 1p (33% and 67%) and 22q (40% and 33%). In addition, endocervical-type adenocarcinoma frequently (> or = 30%) showed LOH on 18p (71%), 19q (50%), 19p (38%) and 16q (38%), whereas endometrioid-type adenocarcinoma frequently showed LOH on 10q (43%) and 5q (40%). LOH was only sporadically detected on 9q, 18q, or 21q in 3 of 7 cases of "pure" adenoma malignum. In a case of coexistence of "pure" adenoma malignum and adenocarcinoma in situ (AIS), LOH on 1q, 5p, 11p, 17p, 18p and 18q was detected only in AIS. LOH was accumulated on a number of chromosome arms in the adenocarcinoma at the early developmental stage before stromal invasion. Chromosomal arms that are prone to show LOH appeared to differ between the 2 types of cervical adenocarcinoma. We could suggest that "pure" adenoma malignum is of clonal and neoplastic nature in view of the detection of LOH.

Adenocarcinoma↗