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Mesothelin (MSLN) shows increased expression in various cancer cells. For clinical application of antibodies as a positron emission tomography (PET) imaging reagent, a human shortened antibody is essential both for avoiding redundant immune responses and for providing rapid imaging. Therefore, we cloned a single‐chain fragment of variable regions (scFv) from a human‐derived gene sequence. This was achieved through the construction of a naïve phage library derived from human tonsil lymphocytes. Using a column with human recombinant MSLN, we carried out bio‐panning of phage‐variants by colony formation. We first obtained 120 clones that were subjected to selection in an ELISA using human recombinant MSLN as a solid phase antigen, and 15 phage clones of scFv with a different sequence were selected and investigated by flow cytometry (FCM). Then, six variants were selected and the individual scFv gene was synthesized in the VL and VH domains and expressed in Chinese hamster ovary cells. Mammalian cell‐derived human‐origin scFv clones were analyzed by FCM again, and one MSLN highly specific scFv clone was established. PET imaging by 89Zr‐labeled scFv was done in mice bearing xenografts with MSLN‐expressing cancer cells, and tumor legions were successfully visualized. The scFv variant established in the present study may be potentially useful for cancer diagnosis by PET imaging.

The role of octamer-binding transcription factor 4 (OCT4) in human cancer is still debated. Although many studies have been published on human OCT4, determining which of the findings are accurate or which are false-positives is currently challenging. We thus developed the most reliable method to date for highly specific and comprehensive detection of genuine OCT4-transcript variants without false-positive results. Our results provided clear evidence that the transcripts of OCT4A, OCT4B, OCT4B1, and other novel splicing variants are indeed present in many cancer cell lines, but are rarely detected in normal tissue-derived differentiated cells. Using the tagged genomic transgene, we then verified endogenous OCT4A translation in cancer cell subpopulations. Moreover, analysis of possible other protein isoforms by enforced expression of OCT4B variants showed that the B164 isoform, designated human OCT4C, is preferentially produced in a cap-dependent manner. We confirmed that the OCT4C isoform, similar to OCT4A, can transform non-tumorigenic fibroblasts in vitro. Finally, ablation of OCT4-positive cells using promoter-driven diphtheria toxin A in high malignant cancer cells caused a significant decrease in migration and Matrigel invasion. These findings strongly suggest a significant contribution of OCT4 to the phenotype of human cancer cells.

Orientador: Prof. Dr. Valery Shchesnovich Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Física, Santo André, 2020. O principal objetivo deste trabalho foi desenvolver a teoria de distinguibilidade para interferências de N fótons únicos em redes lineares unitária com detectores possuindo resolução temporal para os tempos de chegada (ou seja, detectores mais rápidos do que a duração dos fótons). Foi demonstrado o aparecimento de distinguibilidade parcial para uma interferência com esse esquema de detecção, para o caso em que temos os fótons em estados mistos, onde consideramos os tempos de chegada como sendo parâmetros aleatórios. A análise detalhada foi feita considerando o modelo de fótons com perfis Gaussianos e a distribuição para os tempos de chegada também Gaussiana, o que permite resultados exatos. Foi demonstrado também que a distinguibilidade parcial é muito semelhante à do caso em que temos uma detecção sem registro dos tempos de chegada e os fótons possuem mesmas frequências. Dessa forma, concluímos que a distinguibilidade dos fótons devido aos estados mistos não pode ser compensada pela detecção temporal. Também, a partir deste caso geral em que temos estados mistos e resolução nos tempos de chegada, foram recuperados alguns resultados anteriores publicados em trabalhos na área: i) fótons em estados puros ou ii) detectores sem resolução temporal. The main objective of this work is to develop the distinguishability theory for interferences of N single photons in linear unitary networks, with detectors having temporal resolution of the arrival times (that is, detectors faster than the photon duration). It was demonstrated the appearance of partial distinguishability for an interference with this detection scheme, for the case in which we have photons in mixed states, where we consider the arrival times as being random parameters. The detailed analysis was done considering photons with Gaussian profiles, as well as Gaussian distribution for their arrival times, which allows exact analytical results. It was also demonstrated that partial distinguishability in this scheme is very similar to the case in which we have detection without resolution for the arrival times and the photons having the same frequencies. Thus, we conclude that the photon distinguishability due to mixed states cannot be compensated by the temporal detection. Also, from this general case in which we have mixed states and resolution in the arrival times, some previous results published in the area were recovered: i) photons in pure states or ii) detectors without temporal resolution.

Time saving for emergency patient like as a case of heat stroke is eagerly anticipated especially in recent society of Japan. Though implementation new arterial high-standard road may make a considerable contribution, however in practical management, the way to evaluate in monetary terms such effects those related deeply with human life and health has not been established yet. One possible answer is to put the value of statistical one's life (VSL) into the benefit items, and in nowadays 226 million JPY is recommended by Cabinet Office in Japan nevertheless it has not been justified sufficiently. Therefore in this study, firstly we developed a theoretical model in which one tries to give an account of relationship between the research participants’ age and their WTP for the suggested hypothetical service that has an effect of mortality risk reduction, namely “option”. Actually, WTP is option price itself in this context and perfectly proportional with VSL. Secondly, several types of WTP and VSL are proposed for each generation of the participant. These empirical outcomes show rather consistent with the propositions in theoretical conjecture. Either of WTP of 20s or 30s is the lowest value among generations, in contrast, WTP of over 60 is the firstly or secondly largest value among them nevertheless they might have been retired already and income effect worked not so much. The elderly people seem to be willing to pay more than younger ages to build more safety society. In both viewpoints of theoretical and empirical analysis, WTP and VSL evidently differ among age groups and income groups. We confidently conclude that as the degree of VSL depends heavily on the subject regional circumstances, e.g. economic level, population structure, and so on, sufficient and elaborate preliminary investigation is minimum requirements to road project evaluation.

Patients with advanced hematological malignancies are less likely to be referred to specialist palliative care services compared with patients having solid tumors. It has been reported that one of the most important reasons for the lack of referral is difficulties in the prognostication of terminally ill patients with hematologic malignancies. The study objective was to evaluate the predictive accuracy of the Palliative Prognostic Index (PPI) and the prognostic model developed by Kripp et al in hospitalized patients under the care of a hematologist. Using clinical charts, we retrospectively calculated the above scores. We reviewed the records of 114 patients admitted to the hematology ward. The inclusion criterion was patient with disease considered incurable using standard treatments. The prognostic models were assessed according to the original reports. Using PPI cutoff points of 2 and 4, we divided the patients into 3 groups of significantly different survival times ( P < .01). Moreover, we confirmed the usefulness of predicting survival

ヒト血管内皮前駆細胞(Human endothelial progenitor cells :HEPCs)から分泌される可溶性CD93(sCD93)分子の動態を自主開発した抗ヒトCD93 抗体(mNI-11)を用いて解析した。HEPCs は低濃度であるが、sCD93 分子を培養液中に自然分泌していることがわかった。HEPCs をPKC 活性剤であるPMAで処理したところ、sCD93 分子の分泌は有意に増強した(P < 0.01)。また、PMA 処理の初期段階からsCD93 分泌の増強は認められた。次に、PMA 処理HEPCs にPKC 活性阻害剤であるGo6976 を添加したところ、sCD93 分子の分泌は有意に抑制された(P < 0.01)。一方、HEPCs をアクチンフィラメントの脱重合剤(サイトカラシンE)で処理したところ、sCD93 分子の分泌が有意に増強した(P < 0.01)。HEPCs から分泌されるsCD93 分子は、PKC によるリン酸化とアクチンフィラメントの脱重合が密接に関与していることがわかった。, In this study, we examined the secretion of soluble-form CD93 (sCD93) from human endothelial progenitor cells (HEPCs) expressing cell surface CD93 by enzyme-linked immunoassay (EIA) using CD93 monoclonal antibody (mAb) (mNI-11) established in our laboratories. We found that a small amount of sCD93 was spontaneously secreted into the culture supernatants of HEPCs. Furthermore, significantly (P < 0.01) enhanced secretion of sCD93 was found in the culture supernatants of HEPCs treated with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, which was significantly (P < 0.01) suppressed by treatment of the cells with the protein kinase (PKC) inhibitor Go6976. Interestingly, depolymerization of the actin filaments in the cells by cytochalasin E (CyE) also significantly (P < 0.01) enhanced the sCD93 secretion into the culture supernatants of HEPCs. Taken together, these findings suggest that the sCD93 might serve as a new biomarker for analyzing the biological and immunological functions of HEPCs.

Induced pluripotent stem (iPS) cells possess pluripotency and self-renewal ability. Therefore, iPS cells are expected to be useful in regenerative medicine. However, iPS cells form malignant immature teratomas after transplantation into animals, even after differentiation induction. It has been suggested that undifferentiated cells expressing Nanog that remain after differentiation induction are responsible for teratoma formation. Various methods of removing these undifferentiated cells have therefore been investigated, but few methods involve morphological approaches, which may induce less cell damage. In addition, for cells derived from iPS cells to be applied in regenerative medicine, they must be alive. However, detailed morphological analysis of live undifferentiated cells has not been performed. For the above reasons, we assessed the morphological features of live undifferentiated cells remaining after differentiation induction as a basic investigation into the clinical application of iPS cells. As a result, live undifferentiated cells remaining after differentiation induction exhibited a round or oval cytoplasm about 12 μm in diameter and a nucleus. They exhibited nucleo-cytoplasmic (N/C) ratio of about 60% and eccentric nuclei, and they possessed partially granule-like structures in the cytoplasm and prominent nucleoli. Although they were similar to iPS cells, they were smaller than live iPS cells. Furthermore, very small cells were present among undifferentiated cells after differentiation induction. These results suggest that the removal of undifferentiated cells may be possible using the morphological features of live iPS cells and undifferentiated cells after differentiation induction. In addition, this study supports safe regenerative medicine using iPS cells.

Induced pluripotent stem (iPS) cells are an attractive source for potential cell-replacement therapy. However, transplantation of differentiated products harbors the risk of teratoma formation, presenting a serious health risk. Thus, we characterized Nanog-expressing (undifferentiated) cells remaining after induction of differentiation by cytological examination. To induce differentiation of iPS cells, we generated embryoid bodies (EBs) derived from iPS cells carrying a Nanog–green fluorescent protein(GFP) reporter and then injected GFP-positive and GFP negative EBs into nude mice. GFP-positive EB transplantation resulted in the formation of immature teratoma grade 3, but no tumors were induced by GFP-negative EB. GFP positive cells revealed significantly lower cytoplasmic area and higher nucleus/cytoplasm ratio than those of GFP negative cells. Our results suggest that morphological analysis might be a useful method for distinguishing between tumorigenic and nontumorigenic iPS cells.

Cancer stem cells (CSCs) possess the ability for self-renewal, differentiation, and tumorigenesis and play a role in cancer recurrence and metastasis. CSCs are usually sorted in analysis into side population (SP) cells using ultraviolet (UV) laser (350 nm) excitation; they cannot be stained with Hoechst 33342 because of their efflux ability. However, it is difficult to avoid cell damage using a UV laser. Therefore, we attempted to isolate CSCs using a violet laser (407 nm) excitation to avoid cellular DNA damage. We sorted SP cells and main population (MP) cells from a human endometrial cancer cell line using the FACSAria system equipped with a violet laser and analyzed the biological properties of these cells. SP cells exhibited drug efflux, self-renewal, differentiation abilities, and tumorigenicity. It was found that v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) expression was significantly higher in SP cells than in MP cells. Our results suggest that CSCs exist in the SP fraction sorted using the FACSAria system equipped with a violet laser, which presents a useful tool to isolate small populations of viable putative CSCs from solid tumors and can be used to identify and characterize CSCs.

Objective: It was the aim of this study to evaluate the diagnostic utility of Notch-1 immunocytochemistry in distinguishing endometrial glandular and stromal breakdown (EGBD) from endometrial adenocarcinoma in endometrial cytology. Study Design: Samples of normal endometrium, EGBD and endometrial adenocarcinoma were subjected to immunocytochemical staining for Notch-1, and we examined the labeling index (LI) of Notch-1 (the ratio of intranuclear Notch-1-positive cells to total cells). We compared (1) the Notch-1 LI in normal endometrium, (2) the Notch-1 LI between normal endometrium and endometrial adenocarcinoma, and (3) the Notch-1 LI in normal endometrium, EGBD and endometrial adenocarcinoma. Results: In analysis item 1, the LI of Notch-1 was 32.9 ± 8.4, 19.4 ± 8.2 and 12.5 ± 7.5% in proliferative endometrium, secretory endometrium and atrophic endometrium, respectively. In analysis item 2, the LI of Notch-1 in endometrial adenocarcinoma was 45.2 ± 7.4%, which was significantly higher than that in normal endometrium. In analysis item 3, the LI of Notch-1 in EGBD was 31.3 ± 8.3%, which was significantly lower than that in endometrial adenocarcinoma. Conclusion: In conclusion, Notch-1 immunocytochemistry is a useful method for distinguishing between EGBD and endometrial carcinoma in endometrial cytology.

Peripheral flip chip interconnection on gold plated pads would be required to assemble the chip with surface mount technology (SMT) because the gold pads are sometimes used for SMT. Chip Connection (C2) which uses solder-capped copper pillar bumps on the chip and uses reflow process is an attractive method for ultra fine pitch peripheral flip chip interconnection. 50 μm-pitch interconnection on gold plated pads was made with C2 and the shape of the solder joints was discussed. It was found from a mechanical analysis that the stress in low-k layer would be reduced when the solder did not wet on the sides of copper pillars on the chip. Direct immersion gold (DIG) surface treatment would be attractive for not only compatibility to assemble with surface mount components but also for chip-package interaction improvement.

Y. Aratake, K. Marutsuka, K. Kiyoyama, T. Kuribayashi, T. Miyamoto, K. Yakushiji, S. Ohno, Y. Miyake, T. Sakaguchi, T. K. Kobayashi, A. Okayama, K. Tamura and E. Ohno EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma: implications for immunocytochemistry in FNA cytology Objective: Extracellular matrix metalloproteinase inducer (EMMPRIN) and its induced matrix metalloproteinases (MMPs) play a crucial role in tumour progression, invasion and metastasis. EMMPRIN expression has been demonstrated in several tumours, but its expression profile in thyroid cancer remains unclear. Methods: We evaluated the expression profile of EMMPRIN at various stages of differentiation of thyroid carcinoma, including 20 cases of well-differentiated papillary carcinoma (WDPC), 15 cases of papillary carcinoma with a poorly differentiated carcinoma component (PC/PDC) and four cases with an undifferentiated carcinoma (UDC) component, using paraffin-embedded sections for immunohistochemical stains. Also, we used 32 fine needle aspiration cytology and imprint smears from the same cases for immunocytochemical stains. The staining results were evaluated with a scoring system. Results: Immunohistochemical staining showed that EMMPRIN expression was absent or weak in almost all WDPC specimens, whereas it was moderate or strong in PDC and UDC components. In tumours that showed a gradual morphological transformation from WDPC to PDC components, the expression of EMMPRIN was progressively stronger from the areas of WDPC to those of PDC. WDPC, PC/PDC and UDC had expression scores of 4.9, 45.0 and 245.7, respectively. Results of immunocytochemical staining showed almost the same staining profile as those of immunohistochemical staining. The cytological atypia of EMMPRIN-positive cells was greater than that of negative cells. Conclusion: These results indicated that EMMPRIN expression correlates significantly with the degree of dedifferentiation of thyroid carcinoma. This study demonstrates the feasibility of expression of EMMPRIN using fine needle aspiration samples. Therefore, immunocytochemical analysis of EMMPRIN may be a novel aid to evaluate the differentiation of thyroid carcinoma.

Objective: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. Methods: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. Results: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P

S. Hata, N. Kanomata, Y. Kozuka, M. Fukuya, E. Ohno and T. Moriya Significance of collagenous and mucinous spherulosis in breast cytology specimens Objective: Spherulosis of the breast is a rare but distinct benign morphological entity. As there are few cytological reports of breast spherulosis, the significance of spherulosis among cytological specimens is unclear. The objective was to document cytological aspects of spherulosis. Methods: A total of 3491 consecutive breast fine needle aspiration cytology (FNAC) samples and 69 nipple discharge cytology samples were reviewed. Papanicolaou-stained slides with or without Romanowsky staining were analysed. The corresponding 1926 histological specimens were also reviewed. Results: We detected 17 cases of collagenous spherulosis (CS) and/or mucinous spherulosis (MS) among 3560 breast cytology specimens (0.48%). All samples were from women, who varied in age from 22 to 69 years. CS and/or MS were present in 15 of 3491 FNAC specimens (0.43%) and in two of 69 nipple discharge cytology specimens (2.9%). Corresponding histological specimens were available for 14 of the 17 specimens. Of the 14 specimens, 12 consisted of intraductal papilloma, one of fibroadenoma, and one of fibrocystic change. There was no spherulosis among the 1251 cytological specimens of malignant diseases. Conclusions: Cytological evidence of spherulosis is a good indicator of intraductal papilloma.

To achieve low-cost Blu-ray disc (BD) media, a test line for dual layer media based on the "All Spin Method", which we have previously proposed, was fabricated. All transparent layers (the space layer, the cover layer, and the hard coat) were made of inexpensive UV resin by spin coating. Dual-layer BD read-only memory (BD-ROM) media were manufactured with a cycle time of 4 s, and the characteristics of the media were observed. The results indicated that (1) the variation in total thickness of the transparent layers was within ±2 µm; (2) tilt properties after sudden environmental change and storage at high temperatures were good; (3) reproduced signals showed good jitter values and symbol error rate (SER); (4) reproduced signals were not degraded even after a storage test of 200 h at 80 °C and 85% relative humidity (RH). We have thus confirmed that the manufacturing line employing the All Spin Method has potential for mass production of low cost BD media. The All Spin Method is adaptable not only to the manufacture of BD-ROM but also BD-R (recordable) and BD-RE (rewritable), so it can contribute to decreasing the costs of all types of BD media.

The purpose of the current study was to examine the use of thin-layer cytologic (TLC) preparation compared to conventional cytologic preparation (CCP) in the normal endometrium (proliferative, secretory, atrophic) and endometrial glandular and stromal breakdown (EGBD). During a 6-month period, we compiled 158 cases by collecting a direct endometrial sample using the Uterobrush. The material comprised 40 cases of proliferative endometrium, 42 cases of secretory endometrium, 46 cases of atrophic endometrium, and 30 cases of EGBD. The following points were investigated: (1) number of endometrial epithelial cell clumps; (2) presence of TLC > CCP cases on number of epithelial cell clumps; (3) number of condensed cluster of stromal cells; (4) presence of TLC > CCP cases on number of condensed cluster of stromal cells; (5) presence of metaplastic clumps with irregular protrusion-containing condensed stromal cluster; (6) presence of a clear background; (7) presence of blood vessel in TLC; (8) presence of blood vessel of length more than diameter of a field in object x20 glasses in TLC. (1) In all phases, the number of epithelial cell clumps per a unit area of a preparation of TLC is greater than in CCP. (2) Cells (condensed cluster of stromal cells and metaplastic clumps with irregular protrusion-containing condensed stromal cluster) of useful and adequate numbers for a diagnosis of EGBD were observed in TLC. (3) In all phases, TLC was significantly higher than CCP on the appearance of a clear background. (4) The proliferative endometrium and secretory endometrium were highly significant in comparison with atrophic endometrium and EGBD, respectively, in terms of the occurrence of a blood vessel of length more than diameter of a field in object x20 glasses. Although the preparation area of TLC is smaller than that of CCP, the preparation has a clean background so that an accurate report on the patient's condition is possible. Therefore, TLC preparation is a useful tool for the accurate and reliable diagnosis of normal endometrial phase and EGBD, because the preparation area is confined and identification of the target cell clumps is easy.

本研究は, 不確実性下における意思決定問題について論点整理を行った上で, 多地域動学的最適化モデルによるシミュレーション分析を用いて, 費用便益分析の観点から気候変動安定化シナリオの選択に意思決定基準を適用することを試みるものである. ここでは, いくつかの意思決定基準を示し, 全球規模および日本での気候変動安定化政策への適用を行った. 全球規模では, いずれの意思決定基準を用いても, CO2濃度650ppmシナリオが選択される結果となる. 一方, 日本への適用を行った分析では, 多くの意思決定基準においてCO2濃度650ppmシナリオが選択されるものの, より悲観的な立場を重視する意思決定基準を用いた場合には, より厳しいCO2濃度550ppmシナリオが選択される結果となる.

干潟のような生態系を育む場所が地球温暖化によって破壊され, そこに生息する動植物たちが急速な勢いで絶滅の危機に追いやられている. 本研究では, 地球温暖化対策としての干潟保全に関する費用対効果を検討する際に必要となる貨幣評価原単位の提供を目的として, CVMおよびTCMにより都道府県別の干潟の経済価値を計測した. その結果, CVMによる干潟の環境経済価値は, 一人あたりでは1, 599円/年/人 (39, 976円/人), 日本全国では2, 043億円/年 (51, 066億円) となった. また, TCMによる干潟 (潮干狩り) のレクリエーション価値は, 一回あたりでは2, 099円/回, 日本全国では47.0億円/年 (1, 175億円) となった. そして, 干潟の貨幣評価原単位は全国平均で10, 163円/m2となった.

This study paid attention to the difference of WTP (Willingness to Pay) by the difference of payment unit in CVM (Contingent Valuation Method), and measured the discount ratio which was based on difference between the Annual WTP and the Life WTP, by applying the discount function which was discussed well in behavioral economics as psychological approach. Then, we discussed the time preference of people and the validity of current discount ratio (4% annually) which is being used in evaluation of public works in Japan. This result pointed out the problem that the current discount ratio may have the possibility of over-estimation and/or under-estimation of total benefit which depend on conditions.

BACKGROUND Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. METHODS The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28–51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35–65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47–65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42–73 yrs; average age, 58.9 yrs). RESULTS Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. CONCLUSIONS The results of the current study revealed that cytoarchitectural criteria appear to be more useful for the cytologic assessment of endometrial lesions, especially for the diagnosis of endometrial hyperplasia and Grade 1 adenocarcinoma. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.

Careful cytomorphologic evaluation of abnormal endometrial lesions has made accurate and reproducible microscopic assessment possible. Histopathology of patients with dysfunctional uterine bleeding due to an anovulatory cycle usually contain endometrial glandular and stromal breakdown (EGBD) and papillary metaplasia on the endometrial surface epithelium, if an appropriate sample has been collected. We often recognized abnormal cell clumps in the cytological smears with EGBD cases. They were composed of metaplastic cells, and some irregular small projection figures were observed from the margins of the cell clumps. We describe the quantitation of metaplastic clumps with irregular protrusions (MCIP) in endometrial endocyte samples. The current study presents the cytomorphological characteristics of the metaplastic changes recognized in EGBD cases. During a 7-yr period, 144 cases for which histopathological diagnoses were obtained following endometrial curettage, after collecting a direct endometrial sample using the endocyte. The material comprised 49 cases of normal proliferative endometrium (NPE) (patients aged 28-51, average 39.9), 32 cases of EGBD (patients aged 30-67, average 49.6), and 63 cases of endometrial hyperplasia without atypia (EH) (patients aged 35-65, average 47.7). The following points were investigated: (1) the occurrence of metaplastic cells; (2) the occurrence and the frequency of MCIP; and (3) the occurrence of MCIP that contains condensed stromal clusters. Metaplastic cells were seen in 93.8% of the EGBD cases. Cytomorphologic pattern identified with MCIP was 90.6%, and its frequency showed 16.1%. The occurrence of MCIP that contain condensed stromal clusters (93.1%) showed a strong association in comparison with other lesions, such as NPE and EH. Our data appear to indicate that the appearance of MCIP with condensed stromal clusters originated from the papillary metaplasia, which occurred on the endometrial surface epithelium. The cytologic observation of those cells may be a useful indicator for providing the nature of EGBD endometrium.

Endometrial carcinoma is the most common invasive neoplasm of the female reproductive tract. Early detection and accurate diagnosis of these lesions and its precursor by endometrial cytology is now accepted in Japan and regarded as an effective primary method of evaluating endometrial pathology (atypical hyperplasia or carcinoma). Careful cytomorphologic evaluation of the abnormal endometrial lesions has made possible an accurate and reproducible microscopic assessment. The current study was conducted to determine the significance of endometrial cytology on disordered endometrium associated with anovulation when compared with endometrial hyperplasia. From January 1998 through April 2004, 144 cases on which histopathological diagnoses were obtained by endometrial curettage after taken direct endometrial sample by Endocyte. The materials comprise 49 cases of normal proliferative endometrium, and 63 cases of endometrial hyperplasia without atypia were prepared as control cases. The cytomorphology was examined involving so-called endometrial glandular and stromal breakdown (EGBD). EGBD cases evidenced significant numbers of stromal cells condensed and formed compact nests with hyperchromatic nuclei and little or no cytoplasm. They were often associated with fragmented clusters of endometrial glands with condensed cluster of stromal cells. Both the fragmented cluster of endometrial glands and condensed cluster of stromal cells are a characteristic cytologic feature of EGBD endometrium on the cyto-architectural diagnosis. The combination of these cellular patterns is highly specific to this abnormal pathological condition in EGBD endometrium. To improve the accuracy of the cytodiagnosis, it is important that the cytology of the EGBD endometrium should be diagnosed negative; as a result, we can achieve successful endometrial cytology with cyto-architectural criteria for the endometrial pathology.

By constructing a socioeconomic model within the framework of the multiregional general equilibrium theory, this paper proposes a matrix for an urban transport improvement project that illustrates the relationship between benefit generation and incidence. On this matrix the benefit/loss associated with each sector (household, private firm, absentee landowner, public transport corporation, and government) and associated with each item (transport, land, tax, fare revenue, and project surplus/loss) are indicated clearly, so that the social efficiency and equity of the project can easily be discussed.

BACKGROUND Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated. METHODS Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs). RESULTS Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%). CONCLUSIONS Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background. Cancer (Cancer Cytopathol) 2003;99:247–54. © 2003 American Cancer Society.

This study has proposed an economic valuation model to distinguish between the independent effect and the synergy effect of plural public works in the framework of conjoint analysis, and proposed a new method to allot the synergy effect to each project. From a case study on economic valuation of public works in the remoter mainly rural districts, the result indicates that there exist not only the positive value but also negative value of the synergy effect. When we pay attention to allotment of the synergy effect of each two project, it seems that the allotment ratio does not depend on the ratio of the independent effect of each project.

背景:胃原発小細胞癌はきわめてまれな腫瘍である. 今回, 捺印標本による胃小細胞癌の細胞所見に, 免疫化学的および電子顕微鏡的観察を加えて検討したので報告する.症例:65歳, 男性. 内視鏡検査にて胃体上部後壁に94×70cm大のBorrmann 3型の腫瘤を指摘され, 胃全摘術が施行された. 腫瘍摘出時の捺印細胞所見では, 壊死性背景にN/C比のきわめて高い裸核状小型の腫瘍細胞が, 散在性あるいは木目込み細工様に配列して出現していた. 核はリンパ球よりやや大型で円形または楕円形を呈し, クロマチンは細顆粒状で一部には小型核小体を認めた. 肺小細胞癌に類似した所見であった. 組織所見では楕円形から一部模形の核を有する胞体の乏しい腫瘍細胞が充実性に増殖していた. 細胞と組織の免疫染色で, chromogranin Aやsynaptophysinの神経内分泌系マーカーが陽性を呈した. また, 腫瘍組織の戻し電顕で神経内分泌顆粒が確認されたことから, 小細胞癌と確診された. さらに, 同組織に隣接して認められた中分化型管状腺癌を示す小病巣でも神経内分泌顆粒が認められた.結論:本症例は細胞学的特徴より小細胞癌の細胞診断は可能であった. さらに, 免疫組織化学的および電子顕微鏡的観察により神経内分泌細胞への分化が確認された.

A deep ultra-violet (UV) laser beam recorder (LBR) with 248 nm wavelength was developed to realize a high-density disk. The characteristics of the LBR are the wavelength and the multifunctional design. Among the possible laser wavelengths, 248 nm is the shortest wavelength applicable with Novolac photoresist, and the LBR has both modulation and deflection functions to support various formats flexibly. It was confirmed that the LBR performance was such that a groove of even 0.26 µm track pitch could be recorded, and the shape was observed with a scanning electron microscope (SEM). The disk with a groove of 0.32 µm track pitch recorded by the LBR had a practical deviation in the tracking error signal, and the addressed disk with phase-change material and a 0.1-mm-thick cover layer showed the stable reproduction of the address and a practical jitter at the equivalent density for achieving 25 GB capacity at 120 mm in diameter, on the condition of having a pick-up head with a wavelength of 400 nm and an NA of 0.85.

本研究は, 旅行費用法による環境価値計測の可能性を示すことを目的とし, 環境価値に含まれる各種要素 (利用価値, 随意価値, 遺贈価値, 代位価値, 存在価値) の相関関係から, 利用価値によって環境価値のどの程度が説明できるかを検証した.まず, 各価値には有意な相関関係があり, 各価値が独立していないことを明らかにした.次に, 利用価値と各価値の相関関係より, 利用価値で説明できる部分は, 随意価値の80.17%, 遺贈価値の57.79%, 代位価値の76.60%, 存在価値の36.71%, 合計価値の78.98%であることを示した.したがって, 利用価値以外の環境価値も利用価値で80%程度説明できるため, 利用価値を評価対象とする旅行費用法で環境価値の相当部分が計測できることの可能性が示された.

From the viewpoint of necessity of a new method instead of WTP (willingness to pay) in the CVM, this study adopts the benefit evaluation method by WTW (willingness to work). And it examines the difference between results derived by WTP and WTW through the application to the Furukawa-river environmental improvement project in Shizunai-town, Hokkaido-prefecture. The results indicate that the evaluation by WTW is more stable than the evaluation by WTP, and that the latter has higher numbers of unsatisfied people to the evaluation that the former.

目的:子宮内膜癌におけるcyclin dependent kinase2 (cdk2) とKi-67の発現を腫瘍組織分化度およびp53発現と比較して免疫組織化学的に検討した.方法:子宮内膜腺癌, 類内膜型104症例 (高分化型 (G1) 69症例, 中分化型 (G2) 24症例, 低分化型 (G3) 11症例) を対象とした. 免疫染色はLabeled Streptavidin Biotin法で行い, 陽性率と陽性細胞の分布による染色様式を設定した.成績:cdk2, Ki-67およびp53タンパクはすべて核に陽性所見を示した. 腫瘍分化度ごとの陽性率は, cdk2ではG1で10.9±14.3%, G2で18.4±16.2%, G3で25.6±22.8%, Ki-67ではそれぞれ50.1±23.9%, 53.6±19.9%, 66.3±17.4%であった. cdk2ではG1とG2, G1とG3で, Ki-67ではG1とG3, G2とG3で, 低分化ほど陽性率は有意に高かった. cdk2とp53の間でも有意な正の相関を認めた. cdk2の染色様式はG1でsporadic, G2でpartialが有意に多く, cdk2, Ki-67ともに低分化ほどdiffuseとなる傾向を示した.結論:子宮内膜癌において, 腫瘍細胞の分化度が低下し悪性度が増すとcdk2およびKi-67の発現は増加し, さらに染色様式もdiffuseとなる傾向が示された.

目的:北里大学病院では, 細胞異型のみならず構造異型を重視して内膜細胞診の判定を行ってきた.そこでわれわれの判定基準に従って細胞診断を施行した症例を対象に, 体癌症例の細胞診成績, クラスIII以上と判定した症例の組織所見, 内膜細胞診判定基準に関して検討した.対象・方法:1988年から1997年に治療した体癌297例および複雑型子宮内膜異型増殖症22例と, 同期間中に内膜細胞診でクラスIII以上と診断された1,955例である.細胞はエンドサイトで採取し, スライドグラスに直接塗抹したものを用いた.成績:体癌, 複雑型異型増殖症における偽陰性率は各3.4%, 18.2%であった.体癌の組織型別の偽陰性率は, G1, G2類内膜腺癌, 癌肉腫でそれぞれ4.7%, 3.7%, 8.3%で, この他の組織型では偽陰性症例を経験しなかった.G1類内膜腺癌では筋層浸潤の深さにかかわらず偽陰性症例を認めた.クラスIII以上の1,324例では, 内膜細胞診の前後3ヵ月以内に組織診がなされていた.クラスIIIからは241例の内膜増殖症と41例の体癌が, クラスIV, Vからは各6例, 266例が発見された.結論:内膜細胞診の判定では, 構造異型に着目することが重要である.

タイは海面上昇に対して非常に脆弱な国の一つである.本研究は一般均衡理論に基づく社会経済モデルである擬似SCGE (多地域応用一般均衡) モデルを構築し, 本モデルを用いてタイにおける海面上昇による土地損失の経済的影響を評価した.その結果, GDP (国内総生産) は, 50cmおよび100cmの海面上昇により, それぞれ0.361%および0.685%の減少であることがわかった.地域別に見るとバンコク都市圏における生産額の減少分が最も著しく (総被害額の約61%), また産業別に見ると製造業の生産額の減少分が最も著しくなる (総被害額の約38%).

The clinical course and pathological findings of 3 rare cases of androgen-producing ovarian tumors are presented. The ages of the 3 patients (Cases 1, 2, and 3, respectively) were 43, 34, and 57 years, respectively. Their preoperative serum testosterone levels were 506, 491, and 231 ng/dl, respectively. The pathological diagnoses of Cases 1, 2, and 3 were a Sertoli-stromal cell tumor of intermediate differentiation, a stromal tumor containing Leydig cells, and a stromal tumor with minor sex cord elements, respectively. Patient 1 experienced a recurrence, of a lesion at the vaginal stump 1 year and 2 months after the initial surgery. The clinical courses of Cases 2 and 3 have been non-contributory.

The environment value is divided into several values; use value (UV), option value (OV), vicarious value (VV), bequest value (BV), existence value (EV) and ecosystem value (EcoV). This study tried to measure the environmental improvement benefits by the water purification project at the ISE-Bay Area, which is a prominent bay in Japan. By using the contingent valuation method (CVM) and the zone travel cost method (ZTCM), all environment values improved by the project were measured, and difference between results of two methods were examined. The CVM results indicated that the benefits is 59. 9 [billion yen a pear], where UV/OV/VV/BV/EV/Eco V are 9. 5/9. 4/8. 7/10. 2/10. 4/11.7 [billion yen a pear] respectively. The ZTCM results indicate that the benefits is 41. 6 [billion yena pear], which includes UV only and is about four times of UV evaluated by the CVM.

われわれは高悪性度子宮内膜問質肉腫の1例を経験し, その細胞像と核分裂像の出現頻度にっいて検討したので報告する. 症例は65歳, 主訴は不正性器出血, 下腹部痛であり, 臨床的に子宮肉腫が疑われ手術が施行された. 手術標本から採取した捺印細胞診における細胞学的特徴は (1) 内膜問質細胞に類似した細胞の多数出現,(2) 比較的均一な小型から中型の腫瘍細胞,(3) 細穎粒状で増量するクロマチン,(4) 切れ込みやくびれのある不整形核の出現,(5) 一定の分化傾向を示さない,(6) 多数の核分裂像, であり, 子宮内膜問質肉腫 (ESS) と細胞診断された. また, 本症例は免疫細胞・組織化学でVimentinが陽性であった. 組織所見では高悪性度子宮内膜問質肉腫と診断された. さらに, 捺印標本においても組織標本と同様にESSの悪性度を判定できるか否かの検討を行った結果, 核分裂像の出現率は組織診標本0.42%(76±8.0/10HPF), 細胞診標本0.49%(19±0.0/10HPF) とほぼ一致した. このことより, 捺印標本の核分裂像数を計測することはESSの悪性度の推定に有効であると考えられた.

To clarify the mechanism of eosinophilia in adult T-cell leukemia (ATL), we studied three ATL patients having marked eosinophilia. Eosinophil-predominant colony-stimulating activity was detected in the serum of one patient and in the conditioned media (CM) from cultured ATL cells from two patients. Soluble interleukin 5 (IL-5), but no interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), was detected in sera from all patients. On the other hand, GM-CSF was produced in vitro by ATL cells from all cases, whereas detectable IL-3 and IL-5 was produced by cells from only one, suggesting that in the other two cases, the serum IL-5 was produced by the normal reacting lymphocytes. The fact that no patient showed marked neutrophilia supports the possibility that IL-5 may have a leading role in the development of eosinophilia, with GM-CSF produced by ATL cells playing a complementary role.