bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep habits of students attending elementary schools, and junior and senior high schools in Akita prefecture
Authors: TAKEMURA TAKAUBU , FUNAKI KENSAKU , KANBAYASHI TAKASHI , KAWAMOTO KENTARO , TSUTSUI KOU , SAITO YASUSHI , AIZAWA RIKA , INOMATA SHOKO , SHIMIZU TETSUO
Published: March 2003

Abstract It is widely accepted that students in Japan sleep fewer hours than what they actually need. However, epidemiological data on sleep habits among students are scarce. The sleep habits and related problems among 1650 students in Akita prefecture were studied. The results revealed that schoolchildren attending elementary schools seemed to sleep for a sufficient number of hours, whereas students attending junior or senior high schools were not sleeping enough. In particular, approximately half of the students attending senior high schools answered that they slept 6 h or less on weekdays and nodded off during classes more than twice a week.
Influence of arousal level for functional magnetic resonance imaging (fMRI) study: Simultaneous recording of fMRI and electroencephalogram
Authors: MATSUDA TETSUYA , MATSUURA MASATO , OHKUBO TATSUNOBU , OHKUBO HIROMI , ATSUMI YOSHIKATA , TAMAKI MUNEHISA , TAKAHASHI KAZUMI , MATSUSHIMA EISUKE , KOJIMA TAKUYA
Published: March 2003

Abstract Simultaneous recording of functional MRI (fMRI) and electroencephalogram (EEG) has been applied to several clinical fields, making it possible to monitor the arousal level of the subject during a cognitive task. The study confirmed that activated cerebral areas were different between high and low arousal levels during the smooth‐pursuit eye movement task. When arousal level was high, activations in the parietal eye field, frontal eye field (FEF), supplementary eye field (SMA), visual fields (V1) and occipito–temporal junction (V5) were found. In contrast, when arousal level was low, activations were found only in V1 and FEF. The results indicate that the monitoring of the arousal level of subjects using fMRI and EEG recordings simultaneously is crucial for detecting cortical activations during a cognitive task.
Association of the Ser9Gly polymorphism in the dopamine D3 receptor gene with tardive dyskinesia in Korean schizophrenics
Authors: WOO SUNG‐IL , KIM JAE WON , RHA EUGENE , HAN SUN‐HO , HAHN KYU‐HEE , PARK CHUL‐SOO , SOHN JIN‐WOOK
Published: March 2003

Abstract Tardive dyskinesia (TD) is usually regarded as one of the most serious side‐effects of the long‐term usage of neuroleptics due to its high prevalence and potentially irreversible nature. Previously, several genetic polymorphisms were investigated for an association with TD in various ethnic populations. Among them, the Ser9Gly variant in the MscI restriction site of the dopamine D3 receptor gene was reported to be associated with TD. We have investigated the association of Ser9Gly polymorphism of the dopamine D3 receptor gene with TD in Korean schizophrenics. The frequencies of the genotypes of Ser/Ser, Ser/Gly and Gly/Gly in 54 schizophrenic patients without TD were 21 (38.9%), 33 (61.1%) and 0 (0%), while the corresponding frequencies in 59 schizophrenic patients with TD were 25 (42.4%), 28 (47.5%) and 6 (10.1%). We have found a significant genotypic association of the Gly/Gly genotype with TD in Korean schizophrenics (P = 0.028, two‐tailed Fisher's exact test). However, there was no significant allelic association of the Ser9Gly allele with TD (χ2 = 0.288, d.f. = 1, P = 0.591) and there was no significant difference in the Abnormal Involuntary Movement Scale score between the three genotypic groups (P = 0.071, anova). In conclusion, we suggest that Gly/Gly homozygotes in the MscI polymorphic site of the dopamine D3 receptor gene may cause some change in the function of the dopamine D3 receptor and may be involved the pathogenesis of TD.
Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: A preliminary report
Authors: HAGINO HIROFUMI , SUZUKI MICHIO , MORI KOICHI , NOHARA SHIGERU , YAMASHITA IKIKO , TAKAHASHI TSUTOMU , KUROKAWA KENZO , MATSUI MIE , WATANABE NAOTO , SETO HIKARU , KURACHI MASAYOSHI
Published: March 2003

Previous research has found frontal lobe involvement in memory impairment in schizophrenia. In the present study, proton magnetic resonance spectroscopy was performed in 13 young patients with schizophrenia and 13 normal control subjects. Spectra were obtained from a voxel of 2 × 2 × 1.5 cm3 in the bilateral inferior frontal gyrus and thalamus. Subjects were given a verbal learning task and stimulus category repetition (SCR) was calculated from the performance of the task. Significantly reduced N‐acetylaspartate (NAA)/choline‐containing compounds ratios were found in the left inferior frontal cortex of patients compared with controls. The total number of words recalled by patients was significantly lower than that recalled by controls. In all subjects, SCR scores were positively correlated with NAA/phosphocreatine ratios of the left inferior frontal cortex, which showed a trend towards a decrease in patients. These results support the notion of metabolic abnormalities in the left inferior frontal region related to verbal memory deficits in patients with schizophrenia.
The neurotic versus delusional subtype of taijin‐kyofu‐sho: Their DSM diagnoses
Authors: NAKAMURA KEI , KITANISHI KENJI , MIYAKE YUKO , HASHIMOTO KAZUYUKI , KUBOTA MIKIKO
Published: March 2003

The main purpose of the present study was to investigate the diagnostic concepts of taijin‐kyofu‐sho (TKS) and social phobia, by comparing the clinical diagnosis of TKS and the operational diagnosis of Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised; DSM‐III‐R). Three evaluators conducted semistructured interview for DSM‐III‐R (SCID axis I and II, the Japanese version) to 88 outpatients who visited Jikei University Daisan Hospital, Japan, over a period of 1 year, requesting Morita therapy. The patients were also independently diagnosed by three psychiatrists to identify TKS. A total of 65.8% of 38 cases of TKS were diagnosed as social phobia. Among the neurotic TKS cases, the percentage was high at 81.5%, while among the delusional TKS cases it was 27.3%. A total of 42.1% of the TKS cases were diagnosed as mood disorder; 60.5% of the TKS cases presented some axis II disorders, among which avoidant personality disorder was the most prevalent (31.6%). There was no significant difference between the neurotic and delusional subtypes of TKS, regarding comorbidity with axis I diagnoses. As for axis II diagnoses, delusional TKS patients had a higher rate of comorbidity with paranoid personality disorder, although they demonstrated very similar trends in comorbidity with all other personality disorders. In the diagnostic system of DSM‐III‐R, it is highly likely that the neurotic and delusional subtypes of TKS will be seen to correspond to different diagnostic categories.
19F‐magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoate
Authors: SASSA TAKESHI , SUHARA TETSUYA , IKEHIRA HIROO , OBATA TAKAYUKI , GIRARD FRANCK , TANADA SHUJI , OKUBO YOSHIRO
Published: March 2003

Haloperidol decanoate is widely used in the maintenance treatment of schizophrenia and other psychotic disorders, but knowledge concerning its pharmacokinetics at the injected region is very limited. Because the chemical structure of haloperidol contains fluorine, in vivo19F‐magnetic resonance (MR) spectroscopy (repetition time (TR) = 1 s) and chemical shift imaging (CSI; TR  = 1 s, pixel size = 15 × 15 mm) were performed in schizophrenic patients who were treated with haloperidol decanoate (three men and one woman) to measure its diachronic change at the injection point and visualize its local distribution after intramuscular injection. 19F signals (T1 time = 365 ms) were obtained at the haloperidol decanoate‐injected region. The decrease rate of the signal‐to‐noise ratio (SNR) by 19F‐MR spectroscopy seemed large in comparison with that of the plasma haloperidol concentration. The distribution was clearly visualized by 19F‐CSI for a few days after the injection, but after 1 week could no longer be seen. Although the slow‐release characteristics of depot neuroleptics have been explained by the slow diffusion of esterified neuroleptics from the oil vehicle, this result may suggest that there are other mechanisms involved in maintaining the plasma haloperidol concentration. In vivo19F‐MR spectroscopy and CSI are potentially applicable for the pharmacokinetic analysis of haloperidol and other drugs containing fluorine in their structure.
CD95 ligand is expressed in Reed–Sternberg cells of Hodgkin’s disease
Authors: Sakuma Isao , Yoshino Tadashi , Omonishi Kunihiro , Nishiuchi Ritsuo , Teramoto Norihiro , Yanai Hiroyuki , Kawahara Kunimitsu , Kubonishi Ichiro , Matsuo Yoshinobu , Akagi Tadaatsu
Published: March 2003

Reed–Sternberg (RS) cells and their mononuclear variants, Hodgkin’s (H) cells, are considered to be the neoplastic cells of Hodgkin’s disease (HD). The cellular origin of H‐RS cells remains the subject of considerable controversy, although most recent papers have claimed that H‐RS cells are of B cell origin. Recently, however, it has been reported that some H‐RS cells express granzyme B, as observed in cytotoxic T cells and/or natural killer cells, which also express CD95 ligand (FasL/APO‐1L). In the present study, the expression of CD95L and granzyme B in H‐RS cells of HD was investigated. CD95L was detected in H‐RS cells in five of nine HD cases (one case of lymphocyte‐rich classical HD, two of these cases of nodular sclerosis type, and two of four cases of mixed cellularity type). All three examined HD cell lines expressed CD95L in the cytoplasm, although cell surface expression was seen only in L428 cells. Three HD cases expressed both CD95L and granzyme B. It was concluded that CD95L is frequently expressed in H‐RS cells, which is one of their notable characteristics; albeit it seems to be irrespective of cell lineage.
Morphological characteristics of lipid accumulation in liver‐constituting cells of acid lipase deficiency rats (Wolman’s disease model rats)
Authors: Kuriwaki Kazumi , Yoshida Hiroki
Published: March 2003

Lysosomal acid lipase is a hydrolase essential for the intracellular degradation of cholesteryl esters and triglycerides. In the laboratory, rats with congenital deficiency of lysosomal acid lipase and marked accumulation of cholesteryl ester, cholesterol free and triglyceride in livers (Wolman’s disease rat or Yoshida rat) that corresponded to human Wolman’s disease were found and maintained. The morphological characteristics of accumulated lipids in the livers of affected rats were examined also. Many small lipid droplets and lipid crystals were found in the cytoplasms of hepatocytes and ED1‐positive and ED2‐positive foamy Kupffer’s cells, respectively. Electron microscopically, many electron‐lucent lipid droplets with limiting membrane were found in hepatocytes. Foamy Kupffer’s cells had many multivesicular bodies with limiting membrane, which contained crivilinear bodies, lipid droplets and crystal clefts. At areas of aggregation of foamy Kupffer’s cells forming islets, there were many desmin‐positive Ito cells. Small lipid droplets with limiting membrane were also found in the cytoplasm of Ito cells and endothelial cells. These findings, which were obtained by morphological methods, indicated that triglyceride and both cholesteryl ester and free cholesterol accumulated in lipolysosomes mainly in hepatocytes and Kupffer’s cells, respectively, and suggest that lysosomal acid lipase could participate in dissolution of the membrane.
Pigmented squamous cell carcinoma with dendritic melanocyte colonization in the external auditory canal
Authors: Kamiya Makoto , Maehara Ryoji , Iizuka Syu , Yoshida Takatomo , Yamanouchi Hideo , Yokoo Hideaki , Sasaki Atsushi , Hirato Junko , Nakazato Yoichi
Published: March 2003

A case of pigmented squamous cell carcinoma (SCC) with dendritic melanocyte colonization in the external auditory canal is reported and the previous cases are reviewed. A 65‐year‐old Japanese female was referred with a 7‐year history of otitis. The patient also had a darkly pigmented 9 × 8 mm nodule in the external auditory canal. Microscopically, the tumor was SCC, but in some areas melanin pigments were found in the cytoplasm of the tumor cells. The tumor was thus diagnosed as pigmented SCC. As well as the tumor cells, dendritic‐shaped cells colonized the tumor parenchyma and were immunohistochemically defined as melanocytes. The authors believe this is the first case of pigmented SCC with dendritic melanocyte colonization in the external auditory canal.
p53 immunohistochemistry of ulcerative colitis‐associated with dysplasia and carcinoma
Authors: Sato Akira , Machinami Rikuo
Published: March 2003

In order to evaluate the usefulness of p53 immunohistochemistry (IHC) in the diagnosis of ulcerative colitis‐associated colorectal carcinoma (UCACRC), ordinary paraffin sections were examined in 61 cases with ulcerative colitis (UC) and 29 control cases without UC. Among the 61 cases with UC, 11 were complicated by carcinoma coexisting with dysplasia, three with dysplasia, and two cases with adenoma. There were a total of 38 dysplasias, including 33 low grade dysplasias (LGD) and five mixed low and high grade dysplasias (LGD + HGD). The results of p53 IHC were divided into diffuse, nested, scattered and sporadic patterns for 29 control cases. Diffuse and nested patterns were presumed to reflect mutant forms of p53 protein and were defined as overexpression of p53 protein. In non‐neoplastic mucosa of UC, the frequency of p53 positive tubules was significantly higher in active phase (13.5–17.9%) than in resolving phase (3.9–6.5%) and in remission (0.7–2.4%), regardless of association with neoplasia. Eight of the 37 lesions of dysplasia (21.6%) showed p53 overexpression: 12.5% in LGD and 80.0% in LGD + HGD. The rate of p53 overexpression was significantly higher in UCACRC (90.9%) than in non‐neoplastic mucosa of UC (0%), LGD and sporadic colorectal carcinoma (54.5%), but it did not differ between UCACRC and LGD + HGD. Interestingly, the mucosa without dysplasia showed p53 overexpression in one case of UCACRC. The biopsy specimen taken 4 years before the diagnosis of carcinoma revealed p53 overexpression in another case with UCACRC. These results suggest that p53 abnormalities play an important role in UC‐associated tumorigenesis in its relatively early phase. For the diagnosis of dysplasia and carcinoma in UC, p53 IHC seems to be useful.
Immunohistochemical localization of the bone morphogenetic protein‐6 in salivary pleomorphic adenomas
Authors: Kusafuka Kimihide , Yamaguchi Akira , Kayano Teruo , Takemura Tamiko
Published: March 2003

Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We have found that bone morphogenetic proteins (BMP), especially BMP‐2, may play an important role in ectopic chondrogenesis in this tumor. Bone morphogenetic protein‐6 was reported to be related to the osteogenic metastasis of prostatic carcinomas. The relationship between BMP‐6 expression and chondroid tissue formation is investigated. Twenty‐three pleomorphic adenomas were examined immunohistochemically. The overexpression of BMP‐6 was observed in 10 pleomorphic adenomas of the major salivary glands (43.5%), and no evidence of BMP‐6 expression in any of the nine pleomorphic adenomas of the palate. Bone morphogenetic protein‐6 was immunolocalized in the lacuna cells of the chondroid tissue, in which type II collagen was localized. Bone morphogenetic protein‐6 was expressed in inner ductal cells of the tubulo‐glandular structures in the pleomorphic adenomas. This finding indicates that BMP‐6 may be associated with the differentiation of inner ductal cells. Bone morphogenetic protein‐6 was expressed weakly in neoplastic myoepithelial cells in the myxoid areas, which may be related to the production of extracellular matrices. Bone morphogenetic protein‐6 has a role in chondroid formation, and also tubulo‐glandular differentiation in pleomorphic adenomas. In conclusion, a large portion of pleomorphic adenomas of the salivary gland origin, but not of palate origin, was shown to overexpress BMP‐6 protein.
Host genes controlling the susceptibility and resistance to squamous cell carcinoma of the tongue in a rat model
Authors: Kitano Motoo
Published: March 2003

Development of tongue carcinoma (TC) in rats by 4‐nitroquinoline 1‐oxide (4NQO), a potent carcinogen, is under host genetic control. The inbred Dark‐Agouti (DA) strain rats showed a much higher susceptibility to TC than the Wistar–Furth (WF) strain. The author’s previous study on crosses between two strains postulated a susceptibility gene in DA and a resistance gene in WF rats. This hypothesis was confirmed by the genetic analysis of the backcrosses to either parent and F2 with a simple sequence repeat polymorphism analysis. In the crosses between the DA and WF strains of rats, two major independently segregating host loci that influenced the cancer development by application of 4NQO positively or negatively were identified and mapped. DA rats had a semidominant susceptibility gene, Stc1, closely linked with D19Mit9 on chromosome 19, which was on the segment syntenic to human chromosome 16. In contrast, WF rats had a semidominant resistance gene, Rtc1, closely linked with D1Rat320 on chromosome 1, which is syntenic to human chromosome 11. The presence of other susceptibility and resistance genes on some chromosomes of both DA and WF rats was suspected, and they will be clarified in the near future. These findings provide powerful evidence that chemically induced tongue carcinogenesis is a multigenetic event.
Expression of urokinase‐type plasminogen activator, urokinase‐type plasminogen activator receptor, and plasminogen activator inhibitor‐1 and ‐2 in hepatocellular carcinoma
Authors: Zhou Li , Hayashi Yoshitake , Itoh Takashi , Wang Weiping , Rui Jing an , Itoh Hiroshi
Published: March 2003

It has become more and more clear in recent decades that the plasminogen activation system, which includes urokinase‐type plasminogen activator (uPA), urokinase‐type plasminogen activator receptor (uPAR), plasminogen activator inhibitor (PAI)‐1 and PAI‐2, plays a very important role in the aggressiveness of cancer. Using immunohistochemistry and enzyme‐linked immunosorbent assay (ELISA), the expression of these four components of the uPA system was analyzed in 19 cases of hepatocellular carcinoma (HCC) and 18 cases of the adjacent non‐cancer tissues which all had chronic active hepatitis with liver fibrosis or liver cirrhosis. Four cases of normal liver tissues, as controls for immunohistochemical stains, were obtained from the hepatectomized liver of patients with metastatic cancer in the liver. The positive rates of uPA, uPAR, PAI‐1 and PAI‐2 for immunohistochemical stains in cancer tissues were 78.9, 68.4, 57.9 and 31.6%, respectively. Positive signals were mainly distributed in the cytoplasm of the cancer and in stromal cells. Moreover, the strong stains were chiefly located in the invasive front of the cancer cells. No specific stain was detected in four cases of normal liver tissues. In ELISA, there were significant differences between cancer and non‐cancer tissues in concentration of uPA, uPAR and PAI‐1 (P< 0.0003, 0.0024 and 0.01, respectively), but there was no significant difference in that of PAI‐2 (P= 0.37). These results suggest that uPA, uPAR and PAI‐1 are related to invasion of HCC.
Endomyometriosis arising in the uterosacral ligament: A case report including a literature review and immunohistochemical analysis
Authors: Matsuzaki Sachiko , Murakami Takashi , Sato Shinji , Moriya Takuya , Sasano Hironobu , Yajima Akira
Published: March 2003

We report a case of endomyometriosis arising in the left uterosacral ligament of a 29‐year‐old woman. The central cavity of the uterine‐like mass was lined by pseudo‐stratified columnar epithelium and endometrial stroma. The wall of the cyst consisted of bundles of smooth muscle cells. Immunohistochemical analysis demonstrated both α‐estrogen receptor and progesterone receptor immunoreactivities in the epithelial, stromal and smooth muscle cells. A relatively high proliferating activity was also demonstrated in these cells by Ki‐67 immunostaining. These findings suggest that the mass was hormone dependent and had a relatively rapid evolution.
Incidentally detected liver metastasis of well‐differentiated follicular carcinoma of the thyroid, mimicking ectopic thyroid
Authors: Kondo Tetsuo , Katoh Ryohei , Omata Kosaku , Oyama Toshio , Yagawa Akiharu , Kawaoi Akira
Published: March 2003

A case of incidentally detected liver metastasis of follicular carcinoma of the thyroid, histologically mimicking ectopic thyroid, is described. The patient was a 48‐year‐old woman. A 2‐cm mass was incidentally detected in the left lobe of the liver by abdominal computed tomography (CT) scan. Partial liver resection was performed for diagnosis and treatment. Histologically, the liver nodule was composed of small‐to‐large follicles containing colloid material. The lining epithelium was flat or cuboidal and showed no cellular or nuclear atypia. Immunohistochemical studies for thyroid‐specific proteins, thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of thyroid origin. Therefore, a differential diagnosis of metastasis of well‐differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The patient had a history of subtotal thyroidectomy performed 8 years ago due to a thyroid tumor. The original surgical specimens of the thyroid tumor were diagnosed as follicular adenoma. Additional sections of the specimen were reviewed and an area of convincing vascular invasion was found that was suggestive of follicular carcinoma. Subsequent whole‐body examination failed to find other metastases. It was determined that the liver tumor was metastasized from well‐differentiated follicular carcinoma of the thyroid.
Mesenchymal dysplasia of the placenta
Authors: Ohyama Makiko , Kojyo Tsunemaro , Gotoda Hiroko , Sato Toshihiro , Ijiri Rieko , Tanaka Yukichi
Published: March 2003

A severe case of placental mesenchymal dysplasia occurred in association with intrauterine fetal death (IUFD). The gravida‐1, para‐1 mother was a 26‐year‐old Japanese. The first pregnancy was unremarkable and a healthy female infant was delivered. The present pregnancy had been uneventful until 34 weeks of gestation when IUFD was detected. The 1516‐g (mean ± SD, 2050 ± 387 g) stillborn infant had no external abnormalities and the karyotype was 46,XX. The placenta was markedly enlarged (1050 g; mean ± SD, 452 ± 202 g), and approximately 80% was occupied by extraordinary enlarged villous structures with a myxoid appearance. Histologically, the dysplastic villi had myxoid stroma and a decreased number of, occasionally obliterated, fetal vessels. There was no abnormal trophoblastic proliferation. Large‐sized fetal vessels in the chorionic plate frequently contained organized thrombi. This is the first case of placental mesenchymal dysplasia, which possibly lead to the IUFD.
Molecular mechanism of monocyte predominant infiltration in chronic inflammation: Mediation by a novel monocyte chemotactic factor, S19 ribosomal protein dimer
Authors: Yamamoto Tetsuro
Published: March 2003

A novel monocyte chemotactic factor, a cross‐linked homodimer of S19 ribosomal protein (RP S19) was initially isolated from a rheumatoid arthritis synovial lesion. The RP S19 dimer causes the monocyte specific chemotaxis in vitro and the monocyte predominant infiltration in vivo, via its agonistic and antagonistic effects on the C5a receptors of monocytes and polymorphonuclear leukocytes, respectively. The agonistic effect is attributed to the similarity of regional structures between RP S19 and C5a, the complement C5‐derived leukocyte chemotactic factor, although overall homology of the amino acid sequence between these molecules is only 4%. The antagonistic effect depends upon the C‐terminal portion of RP S19. The RP S19 dimer is produced and released by apoptotic cells, and this dimer recruits monocytes from the circulation to the apoptotic lesion. The infiltrated monocytes/macrophages engulf the apoptotic cells, translocate to regional lymph nodes via lymphatics and present the antigenic information of the apoptotic cells to the T cell repertoire. In this manner, the apoptotic cell clearance system connects to the acquired immune system. The innate and acquired immune mechanisms, mediated by the RP S19 dimer, participate in the pathology of inveterate chronic inflammation such as rheumatoid arthritis.
‘Adenomyomatous’ hamartoma of the lung
Authors: Takeshima Yukio , Furukawa Kazuto , Inai Kouki
Published: March 2003

A 53‐year‐old man presented with a lung mass. A segmentectomy of the left lung was performed, and pathologic examination revealed an unusual hamartomatous lesion in the lung, named ‘adenomyomatous hamartoma.’ The tumor was composed of multicysts lined by ciliated pseudostratified bronchial epithelium and smooth muscle overgrowth. The authors have proposed that this is a distinct entity that has not previously been described in the English literature.
Quantitative immunohistochemical evaluation of HER2/neu expression with HercepTestTM in breast carcinoma by image analysis
Authors: Hatanaka Yutaka , Hashizume Kaoru , Kamihara Yuki , Itoh Hitoshi , Tsuda Hitoshi , Osamura R. Yoshiyuki , Tani Yoichi
Published: March 2003

HercepTestTM (DAKO A/S, Glostrup, Denmark) is an immunohistochemical assay that detects HER2/neu gene products, and evaluates the overexpression status of the HER2/neu protein in determining eligibility for the Trastuzumab (HerceptinR, Genentech, San Francisco, CA, USA) therapy. However, practically, interobserver variability of the HER2/neu interpretation of the immunostained results has caused marked disagreement with regard to the intensity of tumor staining. In this study, we quantitated HER2/neu expression by image analysis, and applied this analyzing system to help to minimize interobserver variability of the interpretation of the HercepTestTM. All the immunostained results were scored semiquantitatively on a range of 0 to 3+ in accordance with the criteria described as per the manufacturer’s instructions, and quantitatively evaluated using an image analyzing system with image processing software. Among the 92 cases, 15 were scored as 3+, six were 2+, and 32 were 1+ under intraobservers agreement. When the cases were quantitated, a high correlation was shown between the signal area extracted by image analysis and the corresponding score of staining intensity with the HercepTestTM. By converting the quantitatively extracted data into a scoring system based upon the criteria, the outcome demonstrated a strong concordance with the scoring data obtained from immunostaining. The results indicated that a quantitative scoring system performed by simple image analysis may provide to improve interobserver agreement of the interpretation of the HercepTest TM in clinical practice.
Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor
Authors: Saito Tsuyoshi , Oda Yoshinao , Itakura Eijun , Shiratsuchi Hideki , Kinoshita Yoshiaki , Oshiro Yumi , Tamiya Sadafumi , Hachitanda Yoichi , Iwamoto Yukihide , Tsuneyoshi Masazumi
Published: March 2003

We clinicopathologically evaluated 31 cases of epithelioid sarcoma (ES; 25 ‘classical’ type and six ‘proximal variant’ type) and six cases of malignant rhabdoid tumor (MRT; three extrarenal and three renal). We also did immunohistochemical studies on 12 classical and three proximal variant cases of ES, and six cases of MRT, to clarify the differences in biological behavior in these tumors. E‐cadherin, β‐catenin and CD34 expression was evaluated. We also carried out mutational analysis of exon 3 of the β‐catenin gene by polymerase chain reaction–single‐strand conformation polymorphism analysis. In ES, the 5‐ and 10‐year survival rates were 71.1 and 55.3%, respectively. A high mitotic rate (>15/10 high‐power fields) was significantly correlated with a poor overall survival rate in ES (P = 0.0248). E‐cadherin expression was observed in nine cases (69.2%) of ES and in four cases (66.7%) of MRT. Most of these tumors showed aberrant E‐cadherin expression. Seven cases (46.7%) of ES were positive for CD34, although none of the cases of MRT were CD34 positive. Eleven cases (73.3%) of ES were positive for β‐catenin, which was localized to the cellular membrane, whereas all of the cases of MRT were β‐catenin negative. Mutational analysis for the β‐catenin gene was done in nine cases of ES and six cases of MRT, however, genetic alteration was not found. From our results, we conclude that β‐catenin membranous expression could be a useful marker for distinguishing ES, including the proximal variant, from MRT.
Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genesTSC1andTSC2
Authors: Maruyama Hiroshi , Ohbayashi Chiho , Hino Okio , Tsutsumi Masahiro , Konishi Yoichi
Published: March 2003

Tuberous sclerosis (TSC) is a rare, genetically determined disorder / familial tumor syndrome, currently diagnosed using specific clinical criteria proposed by Gomez, including the presence of multiorgan hamartomas. Pulmonary involvement in TSC is well known as pulmonary lymphangioleiomyomatosis (LAM), which has an incidence of 1–2.3% in TSC patients. LAM has immunohistochemical expression of both smooth‐muscle actin and a monoclonal antibody specific for human melanoma, HMB‐45. It has recently been reported that multifocal micronodular pneumocyte hyperplasia (MMPH) associated with TSC should be considered as a distinct type of lung lesion, whether it occurs with or without LAM. Two predisposing genes have been found in families affected by TSC; approximately half of the families show linkage toTSC1at 9q34.3, and the other half show linkage toTSC2at 16p13.3.TSCgenes are considered to be tumor suppressor genes, and mutations in them may lead to abnormal differentiation and proliferation of cells. Tuberin, theTSC2gene product, has recently been found to be expressed in LAM and MMPH. In this article we discuss the histogenesis and genetic abnormalities of neoplastic lesions associated with TSC, and we review the current understanding of the pathogenesis of pulmonary hamartomatous lesions such as LAM and MMPH in TSC.
Fibrocartilaginous mesenchymoma of the distal femur: Case report and literature review
Authors: Gedikoglu Gokhan , Aksoy M. Cemalettin , Ruacan Sevket
Published: March 2003

A case of a 9‐year‐old boy with fibrocartilaginous mesenchymoma located in the distal femur is presented. Fibrocartilaginous mesenchymoma is a rare tumor. There have been 17 cases reported since 1984. The presenting complaint was pain and local discomfort. Radiological examination showed lytic and sclerotic lesions located in the distal femur. Magnetic resonance imaging showed that there was no soft tissue expansion. Differential diagnosis included fibrocartilaginous dyplasia, dedifferentiated chondrosarcoma, desmoplastic fibroma, fibrosarcoma and low‐grade osteosarcoma. The diagnosis of the tumor in a state hospital would not have been possible. Wide resection of the tumor and resection arthrodesis with an intramedullary nail has yielded good results. The patient has been disease free for 4 years. Pathological diagnosis of this very rare tumor may be challenging; the treatment should be wide resection of the tumor.
Malignant lymphoma of bronchus‐associated lymphoid tissue (BALT) coexistent with pulmonary tuberculosis
Authors: Inadome Yukinori , Ikezawa Tsuyoshi , Oyasu Ryoichi , Noguchi Masayuki
Published: March 2003

A case in which malignant lymphoma occurred in association with a tuberculosis focus in a 70‐year‐old man is reported. Surrounding the epithelioid cell granulomas with caseous necrosis was a dense and diffuse monotonous infiltration of atypical lymphoid cells. Acid‐fast bacilli were found in the granulomas and pulmonary tuberculosis was diagnosed. The infiltrating atypical lymphoid cells occasionally invaded the respiratory epithelium producing lymphoepithelial lesions. Immunohistochemically, the lymphoid cells were positive for CD20, and clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction (PCR). We diagnosed the lesion as a pulmonary malignant lymphoma of bronchus‐associated lymphoid tissue (BALT) occurring in the background of tuberculosis. This is the first reported case of pulmonary BALT lymphoma coexistent with pulmonary tuberculosis.
Teratoid carcinosarcoma of the ovary with prominent neuroectodermal differentiation
Authors: Tanimoto Akihide , Arima Nobuyuki , Hayashi Ryunosuke , Hamada Tetsuo , Matsuki Yasumasa , Sasaguri Yasuyuki
Published: March 2003

We present what we believe to be only the second report of ovarian teratoid carcinosarcoma. The patient, a 59‐year‐old woman, was admitted to hospital complaining of a pelvic mass and of abdominal fullness. Advanced ovarian cancer was diagnosed, and a tumorectomy was done. The tumor occupied the pelvis, and metastasis was found in the liver and spleen. The solid tumor was composed of chondrosarcoma, squamous cell carcinoma, adenocarcinoma and malignant neuroectodermal components, which contained ganglioneuroblastoma‐like and medulloepithelioma‐like areas. Immunohistochemically, the neuroectodermal cells were positive for both neural and epithelial markers. This ovarian tumor consisted of frankly malignant components, with prominent neuroectodermal elements mixed with epithelial and mesenchymal elements in an organoid fashion; a quite rare tumor.
Pancreatic granular cell tumor combined with carcinoma in situ
Authors: Nojiri Takuya , Unemura Yasuki , Hashimoto Katsuyuki , Yamazaki Yoji , Ikegami Masahiro
Published: March 2003

A 58‐year‐old man was treated for a granular cell tumor (GCT) of the pancreas; a very rarely occurring tumor. The patient, who had been followed for 6 years due to alcoholic hepatitis, chronic pancreatitis and elevated carcinoembryonic antigen (CEA) levels from smoking, was admitted to our hospital for evaluation of back pain, diarrhea and constipation. The patient was diagnosed as having pancreatic head cancer using clinical imaging studies, and a pylorus‐preserving pancreatico‐duodenectomy was done. In the resected specimen, a white tumor measuring 13 mm in diameter was observed at the pancreatic head, and there was marked fibrous change surrounding the tumor. The microscopic appearance of the pancreas showed atrophy of acinar cells, fibrosis, and dilatation of the main pancreatic duct (MPD). Within the tumor were oval cells with low‐grade atypia and an increased number of diffuse eosinophilic granules. Neither mitosis nor invasive findings were observed. Periodic acid–Schiff staining and immunohistochemical staining for the S‐100 protein were positive, thus the tumor was diagnosed as a benign GCT. In addition, carcinoma in situ was found at the dilatated MPD. Therefore, this patient was diagnosed as having GCT with carcinoma in situ of the pancreas. To the best of our knowledge, this is only the fourth case of GCT of the pancreas to be reported.
Herpesvirus (HSV‐1, EBV and CMV) infections in atherosclerotic compared with non‐atherosclerotic aortic tissue
Authors: Shi Yu , Tokunaga Osamu
Published: March 2003

The viral nucleic acid of herpes simplex virus type 1 (HSV‐1), Epstein–Barr virus (EBV) and cytomegalovirus (CMV) was studied by polymerase chain reaction (PCR), Southern blotting and in situ hybridization (ISH) in aortic tissues from 33 autopsies. In 23 cases involving persons who ranged from 23 weeks to 75 years of age at the time of death, the tissue was histologically non‐atherosclerotic. Of these 23, aortic tissues tested positive for HSV‐1 in 13%, for EBV in 13% and for CMV in 4%. In the other 10 cases involving persons who were 53–75 years old at death, atherosclerotic aortic tissue tested positive for HSV‐1 in 80%, for EBV in 80% and for CMV in 40%. Neither double nor triple infections occurred in the non‐atherosclerotic group, whereas six of 10 were positive for two viruses, and two of 10 were positive for three viruses in the atherosclerotic group. By in situ hybridization, the viruses were localized in cells morphologically consistent with endothelial cells and smooth muscle cells. We detected HSV‐1, EBV and CMV DNA in cells in the upper portion of the non‐atherosclerotic aortic wall, whereas viral DNA was detected more extensively in atherosclerotic lesions than in non‐atherosclerotic tissue. We also are the first to show the existence of EBV DNA in the human aortic wall. In conclusion, we suggest that the high incidence and kinds of herpesviruses are related to the high incidence of atherosclerosis.
Diffuse pagetoid squamous cell carcinoma of the esophagus combined with choriocarcinoma and mucoepidermoid carcinoma: An autopsy case report
Authors: Ishihara Akira , Mori Takashi , Koono Masashi
Published: March 2003

Esophageal squamous cell carcinoma in situ (SCCIS) with diffuse pagetoid features is a recently recognized rare variant of squamous cell carcinoma. A histopathological study of a specimen from a 70‐year‐old male Japanese patient is reported. The patient died of respiratory failure due to rapidly progressing metastatic pulmonary tumors of unknown origin 73 days after the onset of hemosputum. Autopsy disclosed widespread metastasis of choriocarcinoma in the absence of tumors of the testes or other common sites of germ cell tumors. Elevation of human chorionic gonadotropin (hCG‐β) levels was later detected in the stored serum. Serial histological evaluation of the entire esophagus revealed a small primary site of choriocarcinoma in a background of diffuse SCCIS, mainly of pagetoid type, accompanied by several small foci of submucosally invasive squamous cell carcinoma and primary mucoepidermoid carcinoma. These stimulated nodal metastasis independently of the choriocarcinoma. The SCCIS did not alter the gross mucosal appearance. This is the first reported case of diffuse pagetoid SCCIS combined with choriocarcinoma. Morphological findings and previous studies suggest that the extensive SCCIS of the esophagus resulted from pagetoid spread of tumor cells. The invasive squamous cell carcinoma, mucoepidermoid carcinoma and choriocarcinoma are suggested to have originated from the overlying SCCIS.
Mixed neuronal–glial tumor of the digestive tract: Distinctive entity from gastrointestinal stromal tumor?
Authors: Chambonniere Marie‐Laure , Mosnier‐Damet Michèle , Cavillon Christophe , Mosnier Jean‐François
Published: March 2003

A 53‐year‐old‐woman presenting with pelvic discomfort was found to have a 9.5 cm tumor located in the wall of the ileon. Light microscopy showed that the tumor was made of fascicles of plump spindle cells and bizarre epithelioid cells. A cuff of lymphoid cells was also present at the tumor margin. The tumor cells strongly expressed tau protein, neuron‐specific enolase, protein green product 9.5 and glial fibrillary acid protein (GFAP), but did not show positive immunostaining for S‐100 protein, CD34 or CD117. The tumor showed unequivocal ultrastructural evidence of neural differentiation. Skeinoid fibers were scattered throughout the tumor. This is the first mixed neuronal–glial tumor of the digestive tract to be described in the literature. Such histological and immunohistochemical features could be misinterpreted as features of digestive schwannoma. We suggest that this tumor is distinct from gastrointestinal stromal tumors in lacking CD34 and CD117 expression.
Testicular (gonadal stromal) fibroma: Case report and review of the literature
Authors: Deveci M. Salih , Deveci Güzin , Öngürü Önder , Kilciler Mete , Celasun Bülent
Published: March 2003

A 25‐year‐old man presented with complaint of a painless enlargement in his left testis. The solid, encapsulated, circumscribed and grayish–white testicular mass displayed the characteristics of testicular fibroma histologically. It was composed of acellular collagenized plaques and hypercellular areas of fibroblastic spindle cells. Immunohistochemically, the neoplastic cells were positive for vimentin and smooth muscle actin, but not for cytokeratin, S‐100 protein, desmin, CD99/MIC2 (a protein expressed by Sertoli cells and granulosa cells) and CD34. Only 18 cases of testicular (gonadal stromal) fibroma composed exclusively of spindle cells have been reported to date. An additional case of fibroma, which lacks definite neoplastic sex cord elements, and its differential diagnosis from other mesenchymal lesions of testis are discussed here, together with other cases in the literature.
Pathological significance of vascular endothelial growth factor A isoform expression in human cancer
Authors: Nakamura Masato , Abe Yoshiyuki , Tokunaga Tetsuji
Published: March 2003

Vascular endothelial growth factor (VEGF) is a highly specific factor for vascular endothelial cells. Five VEGF‐A isoforms (splice variants 121, 145, 165, 189 and 206) are generated as a result of alternative splicing from a single VEGF‐A gene. These differ in their molecular weights and in biological properties such as their ability to bind to cell‐surface heparan sulfate proteoglycans. Deregulated VEGF‐A expression contributes to the development of solid tumors by promoting tumor angiogenesis. More specifically, VEGF‐A189 expression is related to angiogenesis and prognosis in certain human solid tumors. VEGF‐A189 expression is also related to the xenotransplantability of human cancers into immunodeficient mice in vivo. Consequently, inhibition of VEGF‐A or VEGF‐A189 signaling regulates the development and metastasis of a variety of tumors. This review focuses on recent studies of the mechanisms by which VEGF‐A regulates angiogenesis in the cancer stroma and on our recent findings concerning the potential mechanisms of VEGF‐A189 expression on tumor growth and metastasis.
Extraskeletal osteosarcoma histologically mimicking parosteal osteosarcoma
Authors: Fukunaga Masaharu
Published: March 2003

An extraskeletal osteosarcoma histologically mimicking parosteal osteosarcoma arising in a 63‐year‐old female is described. The intramuscular lesion in the left lower thigh was a 7 × 4 cm, well‐defined mass with marked central calcification and ossification. The tumor was composed predominately of a centrally located osteocartilaginous component and a peripheral, non‐osseous fibrous component. The former was characterized by a complex interanastomosing pattern of woven‐bone trabeculae with small osteocytes and a minor cartilaginous element. The intratrabecular stroma consisted of benign‐appearing fibroblasts. The peripheral fibrous part was characterized by fascicular and interlacing proliferations of spindle cells with mild atypia, rare mitosis and low to moderate cellularity. There were a few scattered foci of proliferating pleomorphic cells, constituting 5% of the tumor, indicating high‐grade transformation. There was no evidence of zoning phenomena, cortical erosion, periosteal reaction or intramedullary involvement. The patient is well without recurrence or metastasis at 12 months follow up. This soft tissue neoplasm, mimicking parosteal osteosarcoma, should be distinguished from other bone‐forming tumors or tumor‐like lesions with which they may be confused. Pathologists and physicians should know the existence of this type of extraskeletal osteosarcoma and treat it as a high‐grade extraskeletal osteosarcoma.
TLS‐CHOP target gene DOL54 expression in liposarcomas and malignant fibrous histiocytomas
Authors: Domoto Hideharu , Hosaka Taisuke , Oikawa Kosuke , Ohbayashi Tetsuya , Ishida Tsuyoshi , Izumi Miki , Iwaya Keiichi , Toguchida Junya , Kuroda Masahiko , Mukai Kiyoshi
Published: March 2003

Downstream of the gene for the liposarcoma‐associated fusion oncoprotein 54 (DOL54) is a target gene of the myxoid liposarcoma and round cell liposarcoma (M‐LPS/RC‐LPS) oncogene, TLS/FUS‐CHOP. The DOL54 gene product is closely associated with adipogenic differentiation. DOL54 overexpression resulted in tumorigenicity when Chinese Hamster Ovary (CHO) cells were injected subcutaneously into nude mice. The biological significance of DOL54 expression for human malignant soft tissue tumors, however, has not yet been investigated. We examined TLS‐CHOP and DOL54 expression in M‐LPS/RC‐LPS, well‐differentiated liposarcoma and malignant fibrous histiocytoma (MFH), a tumor whose cellular origin has not been determined. We observed DOL54 expression in 50% of M‐LPS/RC‐LPS cases (in which TLS‐CHOP was also expressed) and 33% of MFH cases, suggesting that a portion of MFH lesions may either derive from adipocytic precursor cells or have the potential to undergo adipogenic differentiation. In this manner, M‐LPS/RC‐LPS and MFH lesions may share tumorigenic characteristics, resulting from the unscheduled expression of DOL54.
Solitary fibrous tumor with malignant potential arising in sublingual gland
Authors: Ogawa Ikuko , Sato Sunao , Kudo Yasusei , Miyauchi Mutsumi , Sugiyama Masaru , Suei Yoshikazu , Takata Takashi
Published: March 2003

A rare case is described of a solitary fibrous tumor (SFT) with malignant potential arising in the sublingual gland. A 59‐year‐old man presented with a 4‐month history of a slowly enlarging painless mass in the center of the floor of the mouth. The tumor was a well‐demarcated, firm mass with a multicystic lesion. The tumor exhibited highly cellular areas of spindle cells with patternless architecture alternating with hypocellular areas. The tumor cells were positive for CD34 and bcl‐2 as well as vimentin, and negative for epithelial, myogenic, neurogenic and histiocytic markers. The tumor cells formed multiple satellite nodules around dilated ducts in the multicystic lesion, indicating infiltrative growth. In addition, areas exhibiting higher cellularity with increased mitoses were noticed in the satellite nodules, although cellular atypia was not obvious. These findings led to a final diagnosis of SFT with malignant potential. There has been no recurrence or metastasis for 27 months after the surgery. Solitary fibrous tumor of the salivary gland must be differentiated from various spindle cell neoplasms including myogenic, peripheral nerve sheath, fibroblastic and fibro‐histiocytic spindle cell neoplasms, hemangiopericytoma and myoepithelioma. In addition to characteristic morphological features, an immunohistochemical positivity for CD34 and bcl‐2 may aid in the diagnosis of SFT.
Isolation of bioactive compounds in cyanobacteria from Chinese fresh water. 1. Trypsin inhibitor
Authors: Sano Tomoharu , He Jiawan , Liu Yongding , Kaya Kunimitsu
Published: March 2003

A trypsin inhibitor, oscillapeptin d (1), was isolated from Oscillatoria agardhii, the strain isolated from wa‐terbloom samples of Dianchi Lake in Yunnan province in China. The structure was elucidated to be 1 by chemical degradation and 2‐D nuclear magnetic resonance (NMR) analyses. The inhibitor was a 3‐amino‐6‐hy‐droxy‐2‐piperidone (Ahp)‐containing cyclic depsipep‐tide.