bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of sleep choking syndrome improved by the Kampo extract of Hange‐koboku‐to
Authors: HISANAGA AKITO , ITOH TAKASHI , HASEGAWA YUSUKE , EMORI KENJI , KITA TOSHIAKI , OKABE AKIHITO , KURACHI MASAYOSHI
Published: March 2003

Abstract A case of sleep choking syndrome with typical symptoms is presented. A 44‐year‐old Japanese male suffered from multiple episodes of choking, which suddenly appeared with fear of impending death about 30 min after falling asleep almost every night. Overnight polysomnography showed an apnea index of 0.92 events/h, an apnea–hypopnea index of 2.77 events/h, and normal respiration during sleep with the exception of the episodes of apnea and hypopnea. No choking episode occurred in the sleep laboratory. The administration of 500 mg of acetazolamide was ineffective, but the choking episode improved after the administration of Kampo extract of Hange‐koboku‐to (Ban‐xia‐hou‐pu‐tang). Hange‐koboku‐to may be effective in treating choking sensation during sleep as well as during wakefulness.
Facial pattern categories of sleep breathing‐disordered children using Ricketts analysis
Authors: KIKUCHI MAKOTO , HIGURASHI NAOKI , MIYAZAKI SOICHIRO , ITASAKA YOSHIAKI , CHIBA SINTARO , NEZU HIROSHI
Published: March 2003

Abstract The facial patterns of 29 children under the age of 15 years with tonsil and/or adenoid and sleep disorder problems was analysed. The lateral‐cephalograms of these patients was digitized in a zero‐based computer program using Ricketts analysis to examine facial patterns. Results of the analysis were compared with the mean of the control group, n = 41 (9‐year‐old Japanese children). There were significant

differences (P < 0.01–0.001) between the patient group and the control group when comparing the facial axis, lower facial height, mandibular arc, total facial height, and McNamara–Pogonion. The facial pattern of children with sleep breathing disorders was discovered to be the dolico facial pattern.
Blink rate variability in patients with panic disorder: New trial using audiovisual stimulation
Authors: KOJIMA MAKI , SHIOIRI TOSHIKI , HOSOKI TOSHIHIRO , SAKAI MIWAKO , BANDO TAKEHIKO , SOMEYA TOSHIYUKI
Published: March 2003

Several lines of evidence have implicated central dopaminergic pathways in the modulation of spontaneous blink rate (BR). Furthermore, previous studies have indicated a relationship between spontaneous BR and anxiety and/or depression. However, to our knowledge, there is no report on the examination of BR in a group of patients with panic disorder (PD). During the conditions of rest and with audiovisual stimulation, exposed to a video of imaginary experiences, such as driving a motor vehicle or diving into the sea, BR was examined in 11 male patients with PD and compared with the BR of 16 age‐matched normal controls. The BR was significantly higher in PD patients relative to normal controls under both conditions. In particular, the PD group had a higher BR score during the sea scene as relaxation compared with the normal controls. In conclusion, although the sample size was small the present preliminary study, these findings suggest that BR may have potential for application in the assessment of anxiety state, which is consistent with previous studies.
Pathogenesis of schizophrenia: Part II. Temporo‐frontal two‐step hypothesis
Authors: Kurachi Masayoshi
Published: March 2003

Abstract The objective of the present study was to provide a pathophysiological model of the development of schizophrenia. The method used was the selective review of recent findings, including those of animal models from our own department, to clarify the relationship between morphological brain changes and dopamine metabolism, and the pathophysiology of schizophrenia. The results showed that entorhinal cortex‐lesioned animals had increased concentrations of dopamine in the amygdala, and methamphetamine‐induced dopamine release in the amygdala of lesioned rats was significantly enhanced compared with sham‐operated rats. These results and the morphological findings in schizotypal disorder patients support the view that temporal lobe changes may underlie a vulnerability to schizophrenia. Latent dysfunction in these regions may become clinically apparent as positive psychotic symptoms due to additional frontal lobe changes in schizophrenia. For the emergence of positive Schneiderian symptoms, aberrant activity of sociality‐related circuits, including the amygdala was postulated. In conclusion, a temporo‐frontal two‐step hypothesis for the development of schizophrenia was suggested.
Psychosocial adjustment among pediatric cancer patients and their parents
Authors: Chao Chia‐Chen , Chen Sue‐Huei , Wang Chia‐Yu , Wu Yin‐Chang , Yeh Chao‐Hsing
Published: March 2003

Abstract Children with cancer face both physical and psychosocial challenges. However, there is not enough empirical evidence in Taiwan regarding how they and their families cope with their illness. The purpose of the present study was to explore the psychosocial impact of cancer on target children and their families as well as the degree of depression experienced by these children. Twenty‐four pediatric cancer patients, aged 8 through 17 years, completed the Chinese version of Children Depression Inventory (CDI). Both these patients and 18 parents completed questionnaires about their psychosocial adjustment since the diagnosis of cancer. The results showed: (i) patients did not perceive significant changes in their psychosocial adjustment, whereas parents indicated significantly lower mood of patients and a slight decrease in the number of friends; (ii) both parents and siblings showed positive adjustment; and (iii) there was neither significant difference on the CDI scores between the pediatric cancer patients and a normative group, nor significant relationships between patients’ CDI scores and demographic characteristics of both patients and their parents, parenting attitudes, as well as variables related to the illness. Lastly, the results are discussed in terms of issues of methodology and instruments. Possible direction for further investigations is suggested.
Primary pure intratesticular fibrosarcoma
Authors: Fernando Val‐Bernal J. , Azcarretazábal Teresa , Torío Beatriz , Mayorga Marta
Published: March 2003

Testicular sarcoma appears to be a rare stromal tumor usually of indolent course with potential for distant metastases. A pure primary intratesticular fibrosarcoma in a 71‐year‐old male is presented. By the time the tumor became evident metastases had already occurred widely. The course was rapidly fatal. A review of the literature yielded only one case reported previously. The present case illustrates that pure fibrosarcoma occurs occasionally as a stromal tumor and may be associated with a dismal prognosis. The diagnosis of pure fibrosarcoma should be made only after extensive sampling of the testicular tumor to rule out an associated germ cell component. The differential diagnosis also includes the fibroma of gonadal stroma origin and the unclassified sex cord‐stromal tumor with a predominance of spindle cells.
Distribution of sialic acid‐dependent carbohydrate epitope in thyroid tumors: Immunoreactivity of FB21 in paraffin‐embedded tissue sections
Authors: Nozawa Yoshihiro , Ami Hirofumi , Suzuki Shinnichi , Tuchiya Atuo , Abe Rikiya , Abe Masafumi
Published: March 2003

The reactivity of monoclonal antibody FB21, which recognizes a sialic acid‐dependent carbohydrate epitope, was tested with 94 non‐neoplastic and neoplastic thyroid tissue specimens using immunohistochemical methods on formalin‐fixed, paraffin‐embedded tissue sections. These specimens included 11 cases of adenomatous goiter, three cases of Basedow’s disease, 30 cases of follicular adenoma, 20 cases of papillary carcinoma, 15 cases of follicular carcinoma, six cases of medullary carcinoma, and nine cases of anaplastic carcinoma. FB21 reacted with 14 of 15 cases of follicular carcinoma that showed a microfollicular or trabecular pattern, and with nine of 20 cases of papillary carcinoma. A positive reaction was found on the cell surface membranes or apical parts of neoplastic follicles. FB21 also reacted with five of 30 cases of follicular adenoma. These cases showed a follicular pattern and positive staining pattern similar to that in follicular carcinoma. Adenomatous goiters, Basedow’s disease, medullary carcinomas, and anaplastic carcinomas were negative for FB21 reactivity. Although the different reactivities of FB21 with papillary carcinoma and follicular carcinoma remain to be investigated, the high frequency of reactivity with FB21 suggests that it may be useful as a complement to morphological diagnosis in follicular carcinoma.
Marked histiocytosis in the portal tract in a patient with reactive hemophagocytic syndrome: An autopsy case
Authors: Terada Tadashi , Maeta Hiroyuki , Endo Kanenori , Horie Satoshi , Matsunaga Yoshiko , Ohta Tetsuo
Published: March 2003

We report an autopsy case of reactive hemophagocytic syndrome with peculiar liver histology. A 71‐year‐old female was diagnosed as having acute myelogenous leukemia and treated with chemotherapy. During her course, methicillin‐resistant Staphylococcus aureus (MRSA) was noted in blood culture and she was diagnosed as having MRSA sepsis. She died of respiratory failure 5 months after the onset of leukemia and 10 days after the MRSA sepsis. Ante‐mortem liver function tests were within normal ranges. At autopsy, myeloblastic leukemia cells positive for CD13 were present in the bone marrow and, to a much lesser extent, in the spleen and liver. Numerous histiocytes of a bland appearance with erythrophagocytosis were noted in the bone marrow and spleen. The histiocytes were positive for CD68, but negative for S‐100 and lysozymes. In the liver, many histiocytes of bland appearance with erythrophagocytosis and CD68 positivity were present in the portal tracts with no Kupffer cell hyperplasia. There were no hepatocellular degeneration, fatty changes or sinusoidal dilations. We consider that this histiocytosis was associated with MRSA infection and diagnosed this as infection‐associated hemophagocytic syndrome. In previously reported cases, hemophagocytosis in hyperplastic Kupffer cells was the main liver change of reactive hemophagocytic syndrome. The present case suggests that marked histiocytosis in portal tracts only may be a main feature of liver changes in reactive hemophagocytic syndrome and that such cases may not show abnormal liver function tests.
An immunohistochemical study of the mesenchymal and epithelial components of pulmonary chondromatous hamartomas
Authors: Takemura Tamiko , Kusafuka Kimihide , Fujiwara Mutsunori , Masuda Ryo , Furuhata Yoshiaki , Tanaka Isao , Inoue Masaharu
Published: March 2003

Twenty‐five cases of solitary pulmonary chondromatous hamartomas (PCH) were examined by immunohistochemistry to evaluate the mesenchymal and epithelial components. PCH composed of predominantly mature cartilage were designated as C type, those predominantly composed of fibromyxoid tissue as FM type, and those predominantly composed of adipose tissue as A type. FM type PCH revealed various amounts of cartilage in various developmental stages, adipose tissue and fibromyxoid tissue, compared with a uniform pattern of cartilage tissue in C type. The cells of transitional form between spindle cells, stellate cells and chondrocytes were present in FM type. Epithelial components in PCH were bronchial, bronchiolar and cuboidal cells, mostly at the periphery of PCH. S‐100 protein consistently stained chondrocytes, stellate and spindle cells in the fibromyxoid tissue of solitary PCH. Fibroblast growth factor was immunolocalized to chondrocytes, spindle and stellate cells in the fibromyxoid tissue. The collagen type was associated with differentiation from primitive mesenchymal cells to chondrocytes (i.e. type I and III collagen appeared in fibromyxoid matrix and type II collagen in the cartilaginous matrix). Fibronectin coordinately appeared with type I and III collagens. The proliferating cell nuclear antigen labeling index of epithelial cells was comparable to those of neoplastic mesenchymal cells, but it was not significantly different between C type and FM type PCH. The primitive mesenchymal cells in the bronchial walls of the control premature neonates were also observed. This immunohistochemical study showed that the progenitor mesenchymal cells in the bronchial and bronchiolar walls may differentiate along chondrocytes, lipocytes, and smooth muscle cells in PCH and that epithelial proliferation is reactive and closely associated with neoplastic proliferation of the mesenchymal component.
Uterine adenomyoma of endocervical type
Authors: Kuwabara Hiroko , Ohno Masafumi , Moriwaki Syousuke
Published: March 2003

A uterine adenomyoma of endocervical type was presented histopathologically in a 44‐year‐old woman. She had a mural tumor of the uterine endocervix, which showed a well‐circumscribed margin and multiple cysts filled with mucin. Histologically, the tumor was composed of a proliferation of endocervical glands and smooth muscle. The glandular epithelial components were cystic and occasionally papillary, but neither component showed cytological atypia. A differential diagnosis of the uterine endocervical tumor should include adenomyoma of endocervical type.
Prognostic clinicopathologic factors, including immunologic expression in diffuse large B‐cell lymphomas
Authors: Zhang Anmin , Ohshima Koichi , Sato Kensaku , Kanda Motonobu , Suzumiya Junji , Shimazaki Kae , Kawasaki Chika , Kikuchi Masahiro
Published: March 2003

The aim of this study was to assess the clinical significance and potential prognostic value of the expression of a panel of surface markers, proliferating, suppressor and oncogenic proteins in diffuse large B‐cell lymphomas (DLBCL). Biopsies were collected from 158 patients with DLBCL and analyzed immunohistochemically for p53, p21/WAF1, bcl‐2, cyclin‐D1, bcl‐6, mdr, CD5, CD30, epithelial membrane antigen (EMA), Ki‐67 and c‐myc positive tumor cells. Among these, 76 young and middle‐aged patients (20–65 years) were selected to investigate the relationship between protein expression, clinical features, and survival. Survival analysis showed that advanced stage, high lactic dehydrogenase level, and high International Prognostic Index (IPI) were poor prognostic factors associated with a shorter overall survival (OS) and disease‐free survival (DFS) times. A high p53 expression and low bcl‐6 expression were associated with a shorter DFS time. The histological variant type, cyclin‐D1+ CD5+ DLBCL, positive epithelial membrane antigen (EMA+) CD30– DLBCL, high bcl‐2 expression, and low Ki‐67 proliferation activity tended to be associated with worse survival, but the correlations were not statistically significant. In the multivariate analysis, the most significant factors were age, followed by IPI and last p53. The expression of p21/WAF1, mdr, and c‐myc proteins did not influence OS and DFS. The expression of p53 and bcl‐6 proteins may be useful prognostic indicators in DLBCL. Cyclin‐D1+ CD5+ or EMA+ CD30– DLBCL tended to predict a worse survival and may probably bear a significant prognostic value worthy of consideration. Overall, clinical factors appeared to be more important than biologic parameters in determining the prognosis of diffuse large B‐cell lymphomas.
Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti‐H731 antibody
Authors: Yoshinaga Hidetoshi , Matsuhashi Sachiko , Fujiyama Chisato , Masaki Zenjiro
Published: March 2003

The novel gene H731 (approved name: PDCD4 (programmed cell death 4)) has been isolated as an antigen gene of the monoclonal antibody Pr‐28 which recognized a nuclear antigen in proliferating cells. The gene is homologous to the mouse gene (MA‐3/Pdcd4/A7–1) which was associated with apoptosis and was shown to suppress tumor promoter‐induced neoplastic transformation. A polyclonal antibody against H731‐protein derived from an extract of Escherichia coli transformed with an H731 expression plasmid was prepared, and the H731‐protein expression in human normal and tumor cells using the antibody was studied. The staining patterns of asynchronous cultures of human normal fibroblasts (MRC‐5) were heterogeneous but the antigen was accumulated in the nuclei at the G0 phase. On the contrary, the antigen was overproduced and localized in the cytoplasm during the cell cycle in tumor cell lines. Immunohistological studies revealed that the H731‐protein was highly expressed in bladder carcinoma and breast carcinoma tissues compared with the normal tissues so far tested. These results indicated that expression of the H731‐protein was up‐regulated or induced in the proliferative cells. Immunohistological studies also revealed that the protein was abundantly expressed in the small duct epithelial cells of the normal mammary gland.
Angiomyomatous hamartoma and associated stromal lesions in the right inguinal lymph node: A case report
Authors: Sakurai Yoichi , Shoji Mitsutaka , Matsubara Toshiki , Imazu Hiroki , Hasegawa Shigeru , Ochiai Masahiro , Funabiki Takahiko , Mizoguchi Yoshikazu , Kuroda Makoto , Kasahara Masao
Published: March 2003

Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51‐year‐old male patient visited a local hospital because of a right inguinal mass, measuring 3 × 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick‐walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor‐like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick‐walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma.
Retroperitoneal epithelioid angiomyolipoma leading to fatal outcome
Authors: Yokoo Hideaki , Isoda Koji , Nakazato Yoichi , Nakayama Yuko , Suzuki Yoshihiko , Nakamura Takashi , Shinkai Hiroko , Aiba Motohiko
Published: March 2003

Epithelioid angiomyolipoma (AML) is a newly established variant of AML, characterized by monomorphous epithelioid cells that show HMB‐45 immunopositivity, and it often displays aggressive behavior. To date, they have mostly appeared in the kidneys; however, the present autopsy case of a 43‐year‐old female without the stigmata of tuberous sclerosis complex had a huge retroperitoneal mass, accompanied by involvement of the regional lymph nodes. Histopathologically, the tumor was composed of round, polygonal or short spindle‐shaped monomorphous cells with abundant eosinophilic cytoplasm and large nuclei with frequent multinucleation. Mitotic figures were scattered. Mature fat cells and thick‐walled abnormal blood vessels were totally absent. Immunohistochemically, the tumor cells were reactive with HMB‐45 and α‐smooth muscle actin antibodies. In spite of curative surgery and repeated radio‐ and chemotherapy, the tumor continued to grow and brought about the patient's death 4 years after the initial symptoms. At autopsy, the peritoneal cavity was filled with the tumor mass exceeding 5.5 kg. Histopathological features were essentially the same as those of biopsy samples, but the cellular pleomorphism and emperipolesis were more easily identified. This report calls attention to this unusual manifestation of AML in the retroperitoneum and the importance of distinguishing it from sarcomas and/or paragangliomas.
Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and Artepillin C
Authors: Kimoto Tetsuo , Koya Satomi , Hino Keiko , Yamamoto Yukiko , Nomura Yutaka , Micallef Mark J. , Hanaya Toshiharu , Arai Shigeyuki , Ikeda Masao , Kurimoto Masashi
Published: March 2003

The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe‐NTA)‐induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe‐NTA‐induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe‐NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid‐reactive substances (TBARS) or histochemical findings of 4‐hydroxy‐2‐nonenal (4‐HNE)‐modified proteins and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). Repeated injection of Fe‐NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe‐NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe‐NTA in mice.
β‐Catenin expression and mutational analysis in renal cell carcinomas
Authors: Kim Young‐Sik , Kang Yong Koo , Kim Jung Bun , Han Seon Ae , Kim Kwang Il , Paik Seung R.
Published: March 2003

β‐Catenin acts as a downstream transcriptional activator of the Wingless‐Wnt signaling pathway. The β‐catenin‐Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β‐catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β‐catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β‐catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction–single‐strand conformational polymorphism analysis (PCR‐SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of β‐catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The β‐catenin mutation was identified in only one case of conventional renal carcinoma and was a single‐base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that β‐catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β‐catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β‐catenin signaling pathway may partly play a role in the development of conventional RCC.
Angiomatoid (malignant) fibrous histiocytoma: A peculiar low‐grade tumor showing immunophenotypic heterogeneity and ultrastructural variations
Authors: Hasegawa Tadashi , Seki Kunihiko , Ono Kazuo , Hirohashi Setsuo
Published: March 2003

To clarify the cellular differentiation features and facilitate diagnosis of angiomatoid (malignant) fibrous histiocytoma (AFH), four cases of AFH were examined by clinicopathologic, immunohistochemical and ultrastructural analyses. The age of the patients ranged from 10 to 24 years (mean, 17 years) and the sex distribution was equal. All cases were of subcutaneous origin: three arose in the trunk and one in the upper extremity. All patients presented with systemic symptoms, including inflammatory signs and anemia. After a mean follow up of 11 years 3 months, all patients were alive and well, although one patient twice developed local recurrence after surgery. All cases presented as multinodular, cystic and hemorrhagic tumors ranging in size from 4 to 11 cm (mean, 8 cm) and were characterized by sheets of bland spindle or round cells with oval nuclei within a circumscribed nodule often surrounded by a lymphocytic cuff. One tumor showed predominantly round cell morphology similar to Ewing's sarcoma/primitive neuroectodermal tumor. All cases (100%) exhibited immunoreactivity for vimentin, desmin, CD68 and CD57 (Leu‐7). Three cases (75%) were positive for synaptophysin, and reactivity for α‐smooth muscle actin, epithelial membrane antigen, neuron‐specific enolase and CD99 (O‐13) was present in two cases (50%) each. The three cases examined by electron microscopy had a mixture of fibrohistiocytic, myofibroblastic and undifferentiated cells containing cytoplasmic processes and dense‐core granules. It is important for accurate diagnosis of this peculiar soft‐tissue tumor to recognize that it has a variety of immunophenotypes, such as histiocytic, myofibroblastic, epithelial and neural, and may occasionally have a predominantly round cell morphology.
Correlation between genetic alterations and histopathological subtypes in bronchiolo‐alveolar carcinoma and atypical adenomatous hyperplasia of the lung
Authors: Yamasaki Masahiro , Takeshima Yukio , Fujii Satoshi , Kitaguchi Souichi , Matsuura Masahiro , Tagawa Kohei , Inai Kouki
Published: March 2003

Bronchiolo‐alveolar carcinoma (BAC) is a type of lung adenocarcinoma characterized by growth along the alveolar wall. It is divided into two subtypes: sclerosing BAC (SBAC), which has central fibrosis, and non‐sclerosing BAC (NSBAC), which lacks central fibrosis. We compared the genetic alterations in these two types of BAC with those in atypical adenomatous hyperplasia (AAH). There were 39 cases of SBAC, 19 of NSBAC and 20 of AAH. To detect the loss of heterozygosity (LOH) we used the microsatellite markers D3S1234 and D3S1300 on chromosome 3p, IFNA and D9S144 on 9p, and TP53 on 17p. We also used polymerase chain reaction‐SSCP analysis and direct sequencing to examine a point mutation of the p53 gene at exons 5–8. At the TP53 locus, the frequencies of LOH showed a statistical rank‐difference correlation among AAH, NSBAC and SBAC. On chromosomes 3p and 9p there were no statistical differences of LOH among AAH, NSBAC and SBAC. We detected a significant statistical rank‐difference correlation in the p53 mutation among AAH, NSBAC and SBAC. These findings suggest that a process of multistep carcinogenesis from AAH through NSBAC to SBAC might occur in some cases of adenocarcinoma, and LOH of 3p and 9p might be an early event of carcinogenesis, while the p53 mutation might be a later event.
Effects of subtotal resection of the fundus on development of intestinal metaplasia induced by X‐ray irradiation in Donryu rats
Authors: Kinoshita Ken , Watanabe Hiromitsu , Ando Yasumi , Katayama Masanori , Yamamoto Hideki , Hirano Nobuyuki , Yoshikuni Susumu , Yamamoto Takahiro
Published: March 2003

Eight‐week‐old male Crj:Donryu rats underwent subtotal resection of the fundus and X‐ray irradiation. Six months later the animals were autopsied and examined for intestinal metaplasia. The numbers of alkaline phosphatase‐positive foci with the two treatments in combination were significantly increased, compared to the operation alone and non‐treatment groups. Histologically assessed intestinal metaplasia was also increased in the combined treatment group. In conclusion, subtotal resection of the fundus combined with X‐ray irradiation is an effective induction protocol for intestinal metaplasia.
Oncocytic mucoepidermoid carcinoma of the parotid gland: Report of a case with DNA ploidy analysis and review of the literature
Authors: Deveci M. Salih , Deveci Güzin , Günhan Ömer , Finci Rıfkı
Published: March 2003

A 44‐year‐old female presented with a painful mass in the left parotid gland. Histologic examination revealed the characteristic picture of oncocytic mucoepidermoid carcinoma (OMEC) composed mainly of sheets of oncocytic cells with uniform nuclei and eosinophilic cytoplasm, focally smaller epidermoid cells surrounding poorly formed glandular spaces, and a few cystic structures lined by well‐differentiated mucous cells with intracytoplasmic mucin. Immunohistochemical staining with antimitochondrial antibody showed granular cytoplasmic positivity in oncocytic cells. The resulting histogram for DNA ploidy analysis was of diploid type. OMEC of the parotid gland is a recently described rare neoplasm. Only six cases have been previously reported in the literature. For an accurate approach in the management of patients, OMEC should be considered in the differential diagnosis of oncocytic lesions of the parotid gland, most of which are benign.
Sarcomatoid hepatocellular carcinoma with chondroid variant: Case report with immunohistochemical findings
Authors: Fu Yao , Kobayashi Shoji , Kushida Yoshio , Saoo Kousuke , Haba Reiji , Mori Seiji , Miki Hiroshi , Ohmori Masaki
Published: March 2003

A case of sarcomatoid hepatocellular carcinoma (HCC) with a chondroid variant in a 72‐year‐old woman is reported. Histologically, the tumor consisted of typical HCC of adult type, with an adenocarcinoma‐like structure and a sarcomatoid component containing multinodular chondroid foci. Transition from carcinoma to sarcomatoid component was observed. The cells containing mucus were extremely few in adenocarcinoma‐like structures. Immunohistochemically, other than typical HCC, some of the chondroid cells, adenocarcinoma‐like cells and sarcomatoid cells were positive for alpha‐fetoprotein.
Congenital leiomyomatous epulis: A case report with immunohistochemical study
Authors: Takeda Yasunori , Satoh Masanobu , Nakamura Shin‐ichi , Matsumoto Dan
Published: March 2003

The histologic and immunohistochemical findings of an extremely rare case of congenital soft tissue mass on the alveolar ridge in an infant are reported. The lesion clinically mimicked an ordinary congenital epulis (congenital granular cell epulis, granular cell tumor of the newborn); however, histologically it consisted of a conglomerate of spindle‐shaped cells, akin to smooth muscle cells, which formed interlacing and whorled fasciculi. Nerve fibers with myxoid degeneration, capillaries and muscle walled small vessels intermingled with fasciculi of spindle‐shaped cells. The border between the conglomerate of spindle‐shaped cells and the surrounding connective tissue was not evident. Immunohistochemically, most of the spindle‐shaped cells were intensely positive for antibodies to alpha‐smooth muscle actin, HHF‐35 and desmin. These findings suggest that the lesion was composed of mature smooth muscle cells that were of hamartomatous or choristomatous nature. The term ‘congenital leiomyomatous epulis’ is proposed.
Supradiaphragmatic ectopic adrenocorticotropic hormone‐secreting adenoma
Authors: Jung Shin , Kim Jae‐Hyoo , Kim Tae‐Sun , Lee Min‐Cheol , Seo Jeong‐Jin , Park Jae‐Woo , Kang Sam‐Suk
Published: March 2003

A 22‐year‐old woman with Cushing's syndrome, caused by an extremely rare suprasellar ectopic pituitary adenoma, is presented. Magnetic resonance imaging and computed tomography revealed a well‐circumscribed mass in the right suprasellar region. Endocrinological tests showed elevated s‐adrenocorticotropic hormone level and hypercortisolemia. The tumor was totally removed by right subfrontal approach. At the time of the operation, the tumor was in continuity with the distal pituitary stalk but not with the pituitary gland. The diaphragma sellae was intact. Histologic diagnosis of the tumor specimen was confirmed as a pituitary adenoma. After surgical removal of the tumor, continued improvement in the patient's laboratory results and disappearance of her endocrine symptoms strongly indicated the absence of adenoma cells in the pituitary gland or stalk. Six years post‐surgery, there was no evidence of recurrence in the patient's clinical and laboratory examination. This tumor probably originated from aberrant anterior pituitary cells of the pituitary stalk.
Concordance in judgments among c‐erbB‐2 (HER2/neu) overexpression detected by two immunohistochemical tests and gene amplification detected by Southern blot hybridization in breast carcinoma
Authors: Tsuda Hitoshi , Tani Yoichi , Hasegawa Tadashi , Fukutomi Takashi
Published: March 2003

We compared the c‐erbB‐2 protein overexpression status detected by the HercepTestTM (DAKO A/S, Grostrup, Denmark) with another conventional immunohistochemistry system using an anti‐c‐erbB‐2 rabbit polyclonal antibody (Nichirei Co., Tokyo, Japan) and with the c‐erbB‐2 gene amplification status detected by Southern blot hybridization in 101 surgically resected breast carcinomas. According to the criteria for overexpression, recommended by the manufacturer, c‐erbB‐2 overexpression by HercepTestTM was detected in 24 cancers (24%), comprising six score‐2 tumors and 18 score‐3 tumors. The level of agreement in judgment of the HercepTestTM, among three independent observers, was excellent (κ = 0.845). C‐erbB‐2 overexpression by Nichirei's antibody and c‐erbB‐2 gene amplification were detected in 21% and 16% of cases, respectively, and their concordance with HercepTestTM scores of 2–3 was 89% and 90%, respectively. In the score‐3 cases by Hercep TestTM only, the concordance rates with overexpression by Nichirei's immunohistochemistry and with gene amplification were slightly higher, 94% and 93%, respectively. Score‐2 cases by HercepTestTM were mostly judged as negative overexpression by Nichirei's antibody and as no amplification by Southern blot hybridization. The present results showed that HercepTestTM score‐3 detected c‐erbB‐2 overexpression almost optimally as well as the conventional methods and the score‐3 breast carcinomas had clinical and biological implications. Further examination would be necessary to decide the significance of breast cancers of HercepTestTM score 2.
Development and fate of crescentic and granulomatous lesions in rat Masugi nephritis
Authors: Horio Tetsuro
Published: March 2003

It has been observed that with Masugi nephritis in Wistar rats the initiation of endocapillary proliferative changes with macrophage accumulation is usually followed by glomerular sclerosis without extracapillary extension. In the present study, the provocation of an extracapillary lesion was attempted using accelerated Masugi nephritis in Wistar–Kyoto rats. In order to accelerate the accumulation of monocyte/macrophages, the administration of methylcellulose was added in an additional group. The development and fate of extracapillary lesions were analyzed histopathologically and immunohistochemically. As a result, the formation of extracapillary proliferation of granulomatous lesions could be initiated in this model. Granulomatous lesions were composed of CD4+ T cells and CD8+ T cells and monocyte/macrophages including multinucleated giant cells. These inflammatory cells had seemingly escaped from the capillary lumen through the injured glomerular basement membrane and formed cellular and granulomatous crescents. In addition, tenascin was strongly expressed in cellular crescents and was a unique extracellular matrix at this cellular stage. The cellular crescents then progressed to sclerosis with the formation of increased collagenous extracellular matrix. These results suggest that a delayed‐type hypersensitivity plays a role in granulomatous crescent formation, even though the initial glomerular injury was evoked by a humoral antibody.
An autopsy case of giant cell myocarditis probably due to a non‐steroidal anti‐inflammatory drug
Authors: Adachi Yasushi , Yasumizu Ryoji , Hashimoto Futoshi , Otsuka Yasunori , Okamura Akiharu , Kato Yasushi , Oyaizu Haruki , Ikebukuro Kazuya , Fukuhara Shirou , Nakai Yoshihide , Ikehara Susumu
Published: March 2003

An autopsy case of giant cell myocarditis (GCM) in a 74‐year‐old woman is presented. She suffered from hepatic dysfunction, skin eruption and disseminated intravascular coagulation due to the side‐effects of a non‐steroidal anti‐inflammatory drug. After admission, heart failure progressed rapidly, and the patient died suddenly. At autopsy, her heart was slightly enlarged and the heart muscle was thickened with many small whitish nodules. She was diagnosed with GCM because of the infiltration of multinuclear giant cells, histiocytes, eosinophils and lymphocytes into the heart. We did not find any similar lesions in any other organs. Giant cell myocarditis, the etiology of which is not defined, is a rare disease with unfavorable prognosis. This case suggests the possibility of drug‐induced GCM.
Glomerular crescents in renal amyloidosis: An epiphenomenon or distinct pathology?
Authors: Nagata Michio , Shimokama Tatsuro , Harada Atsumi , Koyama Akio , Watanabe Teruo
Published: March 2003

There have been several reports of cases of renal amyloidosis with glomerular crescents. However, it is not clear whether the association is fortuitous or pathogenic related. The present study analyzed 105 cases of renal amyloidosis (61 autopsy cases and 44 biopsy cases) and found glomerular crescents in 14 (13.3%) cases. Among the 14 cases with crescents, a female predominance was noted (male : female, 3 : 11) and rheumatoid arthritis was the most common primary disease of amyloidosis. Immunohistochemical analysis demonstrated amyloid protein of AA type in 12 cases. According to the histologic classification, there were 11 cases of mesangial nodular type, which was almost exclusively accompanied by AA amyloid deposition. Of note, the incidence of crescents neither correlated with the extent of amyloid deposition nor the presence of nephrotic syndrome. By contrast, localization of amyloid deposition was closely related to crescent formation. Moreover, electron microscopic observation displayed rupture of the glomerular basement membrane at the site of amyloid deposition. Our results indicated that glomerular crescents were more frequently associated with renal amyloidosis than previously appreciated. Rupture of the fragile glomerular basement membrane by amyloid deposition, as revealed by immunostaining and electron microscopy, may be the mechanism of crescent formation. We suggest that glomerular crescents are a distinct pathology associated with renal amyloidosis, not fortuitous conditions.
Goblet cell carcinoid of the appendix: Investigation of the expression of β‐catenin and E‐cadherin
Authors: Kuroda Naoto , Mizushima Shigeru , Guo Limei , Jin Yulan , Tao Lihua , Miyazaki Eriko , Toi Makoto , Naruse Keishi , Hiroi Makoto , Enzan Hideaki
Published: March 2003

Goblet cell carcinoids are rare neoplasms that predominantly occur in the appendix. In this report we present a case of goblet cell carcinoid of the appendix. A 58‐year‐old male patient complaining of pain in the right lower quadrant was diagnosed with acute appendicitis and underwent an appendectomy. Histological examination of the resected appendix revealed goblet cell carcinoid. Infiltration of tumor cells beyond the appendix was observed and the surgically resected margin was positive for tumor cells. Carcinoembryonic antigen (CEA) was diffusely detected by immunohistochemistry, and cytokeratin 20, neuron‐specific enolase (NSE), chromogranin A and serotonin were focally observed in the tumor cells. The expression of β‐catenin and E‐cadherin was investigated to compare with that of typical rectal carcinoids (n = 3) and colon adenocarcinomas (n = 3). In normal colonic and rectal mucosae, β‐catenin and E‐cadherin stained positive on the plasma membrane. In the case reported here, β‐catenin showed a preserved expression on the plasma membrane of goblet cell carcinoid; a pattern similar to typical carcinoids rather than to adenocarcinomas. However, E‐cadherin demonstrated a reduced expression on the plasma membrane of the tumor cells. This staining pattern was identical to those both of carcinoids and of adenocarcinomas. These findings suggest the possibility that, in some cases, the adherens junctions of goblet cell carcinoids are similar to those of typical carcinoids rather than to those of adenocarcinomas.
Intravenous leiomyomatosis of the uterus with multiple pulmonary metastases associated with large bullae‐like cyst formation
Authors: Matsumoto Koshi , Yamamoto Taiichi , Hisayoshi Takao , Asano Goro
Published: March 2003

We present a case of uterine intravenous leiomyomatosis associated with multiple pulmonary metastases with bullae‐like cystic change. A 53‐year‐old woman who had undergone hysterectomy 5 years previously underwent an operation for multiple pulmonary nodules with bullae formation. After resection of several large bullae, a subsequent extirpation of the pulmonary nodules was performed, and a pathological examination showed multiple leiomyomatous nodules with occasional cystic change. A review of the previous slides of the uterus and immunohistochemical analysis of the proliferating ability using anti‐Ki‐67 and anti‐proliferating cell nuclear antigen (PCNA) antibodies were performed. Proliferating cells of the uterus had very few mitotic figures for their high cellularity, and the labeling indices of Ki‐67 and PCNA indicated very low levels in both uterine neoplasm and pulmonary nodules. From these findings, an intravenous leiomyomatosis associated with multiple pulmonary metastases was diagnosed.
An autopsy case of pancreatic and ectopic nesidioblastosis
Authors: Yasoshima Hitoshi , Nakata Yasuo , Ohkubo Eriko , Matsuno Yasuko , Sakurai Kazunari , Kubota Akira , Minagawa Kyoko
Published: March 2003

We report an autopsy case of pancreatic and ectopic nesidioblastosis. A five‐month‐old Japanese girl was born at 35 weeks gestation, and showed clinical symptoms of hyper‐insulinemic hypoglycemia before death. At autopsy a tumorous nodule was observed at the portion of the jejunum, 90 cm from Treitz’s ligament. The nodule measured 30 × 20 × 20 mm. The ectopic pancreas, also revealed nesidioblastosis histologically. Immunohistologically, both nesidioblastoses were stained positive for chromogranin A, insulin, glucagon and somatostatin. The proliferating cell nuclear antigen (PCNA) and Ki‐67 indices were less than 4% in the nesidioblastosis. To our knowledge, this is the first reported case of nesidioblastosis demonstrating proliferating activity with PCNA and Ki‐67, and is the third reported case of nesidioblastosis arising in the pancreas and ectopic pancreas.
Three autopsied cases of cystic fibrosis in Japan
Authors: Iwasa Satoshi , Fujiwara Masachika , Nagata Michio , Watanabe Teruo
Published: March 2003

The incidence of cystic fibrosis (CF) is very rare in Japanese, while it is frequent in Caucasians. Here we report on three Japanese cases of CF. One of the patients had consanguineous parents. All three patients initially developed meconium ileus, and hepatobiliary and pancreatic changes became more severe as age increased. The ΔF508 mutation, the most frequent mutation associated with CF in Caucasians, was not found in these patients. To evaluate the relationship between the severity of hepatic lesions and a history of meconium ileus, we examined hepatic lesions in the present three cases, and we reviewed 22 Japanese autopsied cases of CF in the literature. No correlation was found between the incidence of biliary cirrhosis and a history of meconium ileus, because the cases with meconium ileus showed a high mortality during the neonatal period, before biliary cirrhosis developed. The high incidence of meconium ileus in Japanese CF patients may relate to a clinically severe phenotype and reflect a different genetic background between Caucasians and Japanese.
Comparative study of fibrous dysplasia and osteofibrous dysplasia: Histopathological, immunohistochemical, argyrophilic nucleolar organizer region and DNA ploidy analysis
Authors: Maki Masahiko , Saitoh Kiyoshi , Horiuchi Hajime , Morohoshi Toshio , Fukayama Masashi , Machinami Rikuo
Published: March 2003

Fibrous dysplasia and osteofibrous dysplasia are both benign fibro‐osseous lesions of the bone. We retrospectively studied the clinicopathological findings in 90 cases of fibrous dysplasia and 17 cases of osteofibrous dysplasia. In these cases, the expression of proliferating cell nuclear antigen (PCNA) and the presence of argyrophilic nucleolar organizer regions (AgNOR), as well as DNA ploidy, were examined. The bones affected by fibrous dysplasia were the maxilla, femur and frontal bone. Osteofibrous dysplasia occurred exclusively in the tibia or fibula. The average age of patients with fibrous dysplasia (24.0 years) was higher than that of patients with osteofibrous dysplasia (12.9 years). Fibrous dysplasias were divided into four major histological subtypes: Pagetoid, Chinese alphabet, small bone and parallel bone. Bone lining cells, which are known as resting osteoblasts, were seen in some cases of fibrous dysplasia. Cartilage differentiation was not seen in osteofibrous dysplasia. PCNA expression was strongly positive in the nuclei of osteoblasts around the bone trabeculae in osteofibrous dysplasia, but negative in the nuclei of bone lining cells around the bone trabeculae in fibrous dysplasia. The number of AgNOR in osteofibrous dysplasia was slightly higher than that in fibrous dysplasia. Both fibrous dysplasia and osteofibrous dysplasia were diploid. These features suggest that fibrous dysplasia can be differentiated from osteofibrous dysplasia by anatomical site, patient age, histological appearance, cartilage differentiation and PCNA positivity. DNA content by image cytometry is not a useful tool for differentiating these two diseases.
Chromogenic in situ hybridization analysis of HER‐2/neu status in breast carcinoma: Application in screening of patients for trastuzumab (Herceptin®) therapy
Authors: Kumamoto Hiroyuki , Sasano Hironobu , Taniguchi Takahiro , Suzuki Takashi , Moriya Takuya , Ichinohasama Ryo
Published: March 2003

Evaluation of HER‐2/neu status is important in the management of patients with breast carcinoma, especially in determining the possible application of trastuzumab, a humanized anti‐HER‐2/neu monoclonal antibody. Chromogenic in situ hybridization (CISH) detection of the HER‐2/neu oncogene is a newly developed in situ hybridization method that utilizes a robust and unique‐sequence DNA probe labeled with digoxygenin, and sequential incubations with antidigoxygenin fluorescein, antifluorescein peroxidase, and diaminobenzidine. In this study, we examined 20 archival specimens of human breast carcinoma using CISH, and we correlated findings with immunohistochemical findings for HER‐2/neu. HER‐2/neu immunohistochemistry was carried out with HercepTestTM, a standardized immunohistochemical examination system for HER‐2/neu overexpression in surgical pathology specimens. CISH analysis could be done in 18 out of 20 cases examined. Gene copy signals for HER‐2/neu were recognized as intranuclear brown dots in both neoplastic and non‐neoplastic cells. Seven carcinomas showed an increased number or size of signals and were interpreted as being positive for HER‐2/neu amplification. Eight cases were positive with the HercepTestTM. Seven out of eight carcinoma cases found to overexpress immunoreactive HER‐2/neu also demonstrated HER‐2/neu gene amplification following CISH analysis. There was a significant correlation between immunohistochemical and CISH analyses (P< 0.001). We found that CISH was a specific, sensitive and easily applicable method for the detection of HER‐2/neu gene amplification, which may be used together with immunohistochemical examination for the evaluation of patients with breast carcinoma.