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Hemolytic anemia is a rarely occurring manifestation of native valve infective endocarditis. We herein report an afebrile patient with hemolytic anemia caused by Cardiobacterium hominis endocarditis. A 60-year-old Japanese man had a history of aortic root replacement and the gradual onset of general fatigue. He had hemolytic anemia. Blood cultures detected C. hominis. A transthoracic echocardiogram showed aortic valve vegetation and periannular abscess with perforation of the non-coronary cusp. Intravascular hemolysis recovered after antimicrobial therapy, surgical removal of the vegetation and abscess, and aortic valve replacement. Subacute endocarditis should be considered if patients develop hemolytic anemia with signs of chronic inflammation without a fever.

Scleredema is a rare cutaneous mucinosis characterized by diffuse swelling and non-pitting induration. A 63-year-old man reported a 5-year history of skin thickening of the trunk and a 3-week history of dyspnea. Echocardiography revealed diffuse hypokinesis. Skin biopsies obtained from the waist showed thickened dermis with mucin. Myocardial biopsies showed alcian blue-stained tissue between the muscle fibers. The patient was referred to a dermatologist for phototherapy. Cardiomyopathy should be considered in patients with scleredema. Scleredema usually has a good prognosis; however, the mortality risk could be high when accompanied by cardiomyopathy.

Cerebellar outputs originate from the dentate nucleus (DN), project to the primary motor cortex (M1) via the motor thalamus, control M1 activity, and play an essential role in coordinated movements. However, it is unclear when and how the cerebellar outputs contribute to M1 activity. To address this question, we examined the response of M1 neurons to electrical stimulation of the DN and M1 activity during performance of arm-reaching tasks. Based on response patterns to DN stimulation, M1 neurons were classified into facilitation-, suppression-, and no-response-types. During tasks, not only facilitation- and suppression-type M1 neurons, but also no response-type M1 neurons increased or decreased their firing rates in relation to arm reaching movements. However, the firing rates of facilitation- and suppression-type neurons were higher than those of no-response-type neurons during both inter-trial intervals and arm reaching movements. These results imply that cerebellar outputs contribute to both spontaneous and movement-related activity in the M1, which help to maintain muscle tones and execute coordinated movements, although other inputs also contribute to movement-related activity. Pharmacological inactivation of the DN supports this notion, in that DN inactivation reduced both spontaneous firing rates and movement-related activity in the M1.

A 78-year-old Japanese man who had undergone total prostatectomy for prostate cancer (pT3cN1M0, Gleason score 3 + 3) 20 years previously was referred to the Respiratory Medicine Department of our institution because of a 1-week history of chest pain and cough. Computed tomography showed multiple small nodules and mediastinal lymph node enlargement. Bronchoscopy revealed multiple soft polypoid masses and obstruction of the lingular segment. Prostate-specific antigen (PSA) concentrations had increased markedly from 0.48 ng/mL in 2014 to 741 ng/mL in 2018. The diagnosis of prostatic cancer metastases was confirmed by revealing the presence of PSA via immunohistological staining of a bronchoscopically obtained biopsy of one of the masses. The patient had not been attending scheduled follow-up visits for the past 4 years. Treatment with degarelix (a gonadotropin-releasing hormone) was started, and the PSA concentration decreased dramatically (29 ng/mL). Metastases from prostate cancer are rarely first diagnosed two decades after radical prostatectomy. This patient illustrates the importance of obtaining a complete medical history. Keywords: Bronchoscopy, Prostate cancer, Endobronchial metastases, Metastatic lung cancer, PSA

A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor which was first defined by Steiner, et al . in 1957 (1). CLC is thought to be derived from Hering’s canal because tumor glands of CLC are morphologically similar to cholangioles. Recently, Theise, et al . reported that Hering’s canal might be composed of hepatic stem cells (3). In addition, CLC sometimes contains a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component within the tumor. Those findings suggest that CLC might originate from hepatic stem cells. On the other hand, because of its low frequency, clinicopatholigical features of CLC have not been fully clarified yet. We herein report a case of a 71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20, CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as CLC. The diagnostic criteria have not been described clearly, so CLC is difficult to diagnose preoperatively. Further studies are needed to clarify the clinical and clinicopatholigical features of CLC.

Background Although the histologic features of malignant peripheral nerve sheath tumor (MPNST) have been described, the cytologic features of primary pulmonary MPNST have not been reported in the literature. Case We report a case of primary pulmonary MPNST in a 78-year-old man. Follow-up computed tomography of colon cancer, renal cancer, penile cancer and gingival cancer revealed a nodular lesion, 12 mm in diameter, in the right upper lobe of the lung. In frozen section, a diagnosis of malignant neoplasm, not otherwise specified, was rendered for the imprinting specimen and histologic specimen. Imprinting specimens were composed of small cellular aggregates and discohesive neoplastic cells with obvious malignant features. Histologically, spindle cells with pleomorphic nuclei arranged in fascicular patterns and multinucleated tumor giant cells were also observed. More than 25 mitotic figures were observed per 10 high-power fields. Tumor cells were positive only for vimentin and S-100, and the Ki-67 labeling index was 10%. Clinical and imaging investigation failed to identify an alternative primary site. We histologically diagnosed this case as primary pulmonary MPNST. Conclusion MPNST has a varied cytomorphology with frank nuclear atypia showing no definite differentiation. Multinucleated neoplastic giant cells with immunopositivity for S-100 may permit more accurate diagnosis of MPNST.

We report two cases of invasive aspergillosis of the head and neck regions. One patient was a 56-year-old male with invasive aspergillus sinusitis. The other patient was a 14-year-old boy with aspergillus mastoiditis after bone-marrow transplantation. Both cases were inoperable because of vascular invasion by aspergillus, and treatment with antifungal agents was discontinued due to severe side effects. A novel triazole voriconazole (VRCZ) was then used for salvage therapy and successfully treated invasive aspergillosis in both cases. VRCZ is an effective and well tolerated agent to treat invasive aspergillosis of the head and neck regions.

Objective: We compared the duration of ablation and the area of coagulation necrosis between a single ablation method (SAM) and a double ablation method (DAM) with a ’multitined expandable’ electrode (LeVeen 2cm) for radiofrequency ablation (RFA) using pig liver.Method: In the SAM group, ablation was completed after the first roll-off. In the DAM group, an additional ablation was performed to achieve a second roll-off. The comparison was made of the time required for roll-off and the extent of coagulation necrosis between the both groups. The Ellipticity index (EI) quantitatively describes the shape of the general RF ablation zone in the axial plane.Results: There was no statistically significant difference in the interval until the first roll-off between both groups (SAM group: 100.7±24.7 seconds vs DAM group: 103.2±37.7 seconds, P=0.43). In the DAM group, the interval from the start of the additional ablation until the second roll-off was 154.0±86.9 seconds, longer than the interval for the first roll-off (P=0.023). The extent of coagulation necrosis was significantly more extensive in the DAM group (axial diameter, mean±SD, 26.2±2.8mm)×(maximal diameter: 29.3±1.6mm)×(minimal diameter: 26.5±3.6mm) compared to the SAM group with (23.0±3.3mm)×(23.7±3.1mm)×(20.0±2.5mm), respectively. Although there was no statistically significant difference in the EI between both groups, macroscopically, the shape of coagulation necrosis tended to be non-spherical in the SAM group and spherical in the DAM group.Conclusions: The DAM with a ’multitined expandable’ electrode was more extensive with a spherical zone shape compared to the SAM. J. Med. Invest. 54: 28-34, February, 2007

Human cathepsin G (EC 3.4.21.20) has been reported to have the in vitro chemotactic activity for human monocytes. In this study, we examined the role of cathepsin G in monocyte involvement in joint inflammation of rheumatoid arthritis (RA) as a monocyte chemoattractant. Eighteen patients with RA and four patients with osteoarthritis (OA) were used in this study. Thiobenzylester substrate, Succ-Phe-Leu-Phe-S-Bzl, was used to measure the activity of cathepsin G in synovial fluids. Monocyte migration induced by cathepsin G and synovial fluids was assessed by a 48-well microchemotaxis chamber technique. Immunohistochemical staining was performed to determine the cellular origin of cathepsin G in RA synovial tissue. A very low activity of cathepsin G was detected in synovial fluids from patients with OA. On the other hand, significantly increased activity of cathepsin G was detected in patients with RA when compared with the value of OA patients. A considerable monocyte chemotactic activity was detected in the synovial fluid of RA patients, and the activity was partially decreased by the treatment with inhibitors for cathepsin G, alpha1-antichymotrypsin and phenylmethylsulfonyl fluoride. The activity of cathepsin G was significantly correlated with the neutrophil counts in synovial fluids and the concentration of interleukin-6. Immunohistochemical studies showed that cathepsin G was strongly expressed by synovial lining cells, and weakly expressed by macrophages and neutrophils in synovial tissues. This study indicates that the monocyte chemotactic activity of cathepsin G may have a role in the pathogenesis of RA synovial inflammation.

The solitary necrotic nodule of the liver is an uncommon nonmalignant lesion with an uncertain etiology. The lesion was defined as a nodule with a completely necrotic core and fibrous capsule etc. and without a consistency of viable cells. The characteristic features of this benign lesion on the imaging modalities are similar to the metastatic tumor. In this paper we discuss the case of a rapid-growing solitary necrotic nodule of the liver occurring in a patient with chronic renal failure on hemodialysis. The lesion located on the left median lobe of the liver had rapidly enlarged in diameter in the last seven months. Despite some examinations by imaging modalities to confirm the preoperative diagnosis, we were unable to visually confirm. Several histological examinations using a needle biopsy specimen were performed, but the diagnosis was all necrotic tissue. However, we recommended an extended left hepatic lobectomy for this rapid-growing lesion since cholangiocarcinoma with necrosis could be hardly differentiated. Permanent histology revealed that the lesion was solitary necrotic nodule. We consider that permanent histology of the entire lesion is possibly the only accurate method of diagnosis. Since the solitary necrotic nodule does not indicate malignancy, hepatic resection should be performed.

Gastric inverted hyperplastic polyp (IHP) is a rare type of gastric polyp, and is characterized by downward growth of the hyperplastic mucosal components into the submucosa. To the best of our knowledge, 16 gastric IHP cases have been described in the English literature, but the pathogenesis has not been established. We report the clinical and pathological findings of four gastric IHP cases. The lesions were mainly composed of hyperplastic foveolar-type glands with focal cystic dilatation. Pyloric type glands, endocrine cells, acinic cell metaplasia, and smooth muscle bundles were also seen as components of the polyp. Two cases (cases 1 and 4) coexisted with multifocal gastritis cystica profunda (GCP) and gastric adenocarcinoma. Case 4 furthermore exhibited an intermediate form between IHP and GCP. We suggest that IHP may be GCP associated with exaggeratedly hyperplastic and metaplastic changes. In case 4, the coexisting gastric carcinoma was mainly located in the submucosa, whilst the mucosal component was minimal. Five out of twenty reported gastric IHP cases, including our cases, coexisted with gastric adenocarcinoma. These facts would lead us to further investigate the relation between gastric IHP and carcinoma.

Our earlier study revealed that 1- and 3-nitrobenzo[a]pyrene (NBP), 1,6- and 3,6-dinitrobenzo[a]pyrene (DNBP), nitrated derivatives of benzo[a]BP (BP), are present in the environment. These derivatives are potent mutagens for Salmonella tester strains and we have preliminarily reported them to be carcinogenic in F344/DuCrj rats. In this study, the tumorigenic action of 1- and 3-NBP, 1.6- and 3,6-DNBP, and BP induced by subcutaneous injection into rats was found to differ according to the NO2-substitution in the BP structure. The chemicals were suspended in equal volumes of beeswax and tricaprylin, and rats were subcutaneously injected with single doses of 500, 1000, and 2000 microg for 1- and 3-NBP, and of 8, 40, 200, and 1000 microg for 3,6- and 1,6-DNBP, and BP as a positive control. 3,6-DNBP and BP induced tumors in a dose-dependent manner at the injection site. Rats given 1000 microg of 3,6-DNBP (2924 nmol) and BP (3968 nmol) developed subcutaneous tumors at the rate of 70 and 80%, respectively, and those given a minimum dose of 23 nmol for 3.6-DNBP and 32 nmol for BP per rat developed tumors at a rate of 4.8 and 18.2%, respectively. However, rats given 500 and 1000 microg of 1- and 3-NBP did not develop any tumors while those given a high dose, 2000 microg, of each chemical developed tumors at only one of ten animals used. It was concluded, therefore, that these chemicals are weak carcinogens. Histologically, most of the tumors were malignant fibrous histiocytomas. Rats given various doses of 1,6-DNBP did not develop any tumors at the injection site. The failure of 1,6-DNBP to induce tumors may involve its metabolites because of the lower mutagenicity of its reduction products, 1-nitroso-6-NBP and 1-amino-6-NBP. It is suggested, therefore, that tumorigenicities of NBPs and DNBPs differ according to the NO2-substitution on the chemical structure, which may be due to the possible nitroreduction of the chemicals.

The purpose of this paper is to clarify whether copper accumulation in hepatocellular carcinoma (HCC) is a cause of high intensity signal pattern on T1-weighted images (T1-WI) by comparing the histologically proven copper accumulation with MR images. Forty-five surgically resected HCCs were analyzed. Distribution patterns of divalent copper by a modified Timm's method on their maximum cut surfaces were compared with signal patterns on corresponding T1-WI. The degree of copper accumulation in tumor compared with surrounding liver tissue was higher in 6 lesions, equal in 17 lesions, and lower in 22 lesions. High intensity pattern on T1-WI were observed in 3 of 6 lesions (50%), 10 of 17 lesions (59%), and 10 of 22 lesions (45%). Distribution patterns of copper were not correlated with intensity patterns on T1-WI. We conclude that the paramagnetic effect of divalent copper accumulation in HCC is insufficient to influence the MRI.

子宮頸部にはまれに神経内分泌癌が発生することが知られている. 30歳, 妊娠29週の女性の子宮頸部に発生した小細胞性神経内分泌癌の1例を経験したので, 細胞所見を中心に報告した. 患者は不正性器出血を主訴として来院し, 頸部前唇にピンポン玉大の腫瘍が見出されたため, 広範子宮全摘出手術が行われた. 術後, 大量化学療法と末梢血幹細胞移植が施行されたが, 合併症のため約7ヵ月後に死亡した. 擦過細胞診では, 小型で裸核状の腫瘍細胞が壊死物質を背景に孤立散在性ないし結合性の弱い小集塊として認められ, 肺小細胞癌の細胞所見に類似していた. 組織学的に腫瘍細胞は, 胞巣状, 索状ないしリボン状に配列し, 多くの細胞でGrimelius法により好銀顆粒が証明された. 免疫組織化学的に, Chromogranin A, neuron specific enolase, synaptophysinなどの神経性マーカーが陽性を呈しており, 小細胞性神経内分泌癌と診断された. 本腫瘍は, 小細胞性扁平上皮癌や低分化腺癌との鑑別が難しいが, これらの腫瘍より進行が早く悪性度が高いので, 早期に診断し強力な治療を開始することが大切である. 診断上, 細胞診のはたす役割は大きいと考えられた.

We report an autopsy case of Cockayne syndrome (CS). A 40-year-old Japanese woman was admitted to our hospital for cachexia. She had displayed the striking features of CS, including dwarfism, mental retardation, neural deafness, ataxia, intracranial calcifications, and progeria since her childhood. Endocrinological examinations suggested normal pituitary function and a disorder of the hypothalamus or the cerebrum. She died of acute pneumonia at the age of 42. Autopsy findings showed typical abnormalities in the central nervous system compatible with CS; however, no atherosclerotic change was observed in the systemic arteries.

患者は57歳, 男性.43歳時, 結核検診で胸部異常陰影が出現し, 翌年精密検査を受け, 肺結核として治療・経過観察を受けていた.しかし陰影は次第に増大し, 陰影出現から14年目に腺癌と診断され, 手術が行われた.腫瘍は粘液産生性で, 組織像では気管支腺の構造を模倣する腺管型腺癌の部分と乳頭型腺癌の部分が混在していた.

ステロイド投与により肝機能の改善を認めたものの,HCV-RNAが陽転化したAIHの1例を経験した.症例は49歳,男性.平成4年に第二世代HCV抗体陽性を指摘されるも放置されていた.平成6年6月中旬より全身倦怠感が出現するとともに肝機能の増悪を認め,慢性C型肝炎の急性増悪を疑い治療を開始した.トランスアミナーゼ活性の低下は認めたが,総ビリルビンおよびγグロプリンの著明な増加を認めた.血液検査にて抗核抗体および,IgGは著明な高値を示し,肝生検組織所見ではAIHが強く疑われた.さらに分岐DNAプローブ法およびPCR法にてHCV-RNAが陰性であったことよりAIHと診断し,ステロイド治療を開始した.肝機能は徐々に改善したが,その後のウイルス学的再検査でHCV-RNAが著増(108copy/ml)していることが確認された.本症例は自己免疫性肝炎とC型肝炎の関係を考える上で示唆に富む症例と考えられた.

まれな甲状腺腫瘍である硝子化索状腺腫を経験したのでその穿刺細胞像ならびに病理組織学的, 電顕的および免疫組織化学的所見について報告する.症例は38歳女性で, 甲状腺腫瘤の穿刺細胞診にて異型の少ない短紡錘形細胞ではあるが, 核内偽封入体, 核溝を有した細胞が認められたため, 乳頭癌を疑われ, 切除手術が施行された. 切除材料の組織学的検索では, 短紡錘形の細胞が索状に配列し, アミロイド様の間質を伴う像を認め, 電顕的には核内偽封入体, 多量の細胞質内フィラメント, 肥厚した基底膜様構造がみられ, 硝子化索状腺腫と診断した.細胞診上, 硝子化索状腺腫を正診することは容易ではないと思われるが, 乳頭癌と髄様癌の両者の類似像を得た際は, それを鑑別診断にあげる必要があるものと思われた.

d-Amino acid oxidase (DAO) is a peroxisomal flavoenzyme that catalyzes oxidative deamination of a wide range of d-amino acids. Among the possible substrates of DAO in vivo, d-serine is proposed to be a neuromodulator of the N-methyl-d-aspartate (NMDA) type glutamate receptor. The gene for DAO was reported to be associated with schizophrenia. Since DAO is expected to be one of the key enzymes in the regulation of NMDA neurotransmission, the modulation of the enzyme activity is expected to be therapeutical for neuronal disorders. In search of the pathophysiological role of DAO, we analyzed the distribution of DAO mRNA and protein in the rat and human brain. In rat, the distribution of DAO mRNA was newly detected in choroid plexus (CP) epithelial cells in addition to glial cells of pons, medulla oblongata, and especially Bergmann glia of cerebellum. Moreover, to investigate how DAO expression level is altered in schizophrenia, we performed immunohistochemistry in the human brain. In agreement with the results in the rat brain, the immunoreactivity for DAO was detected in glial cells of rhombencephalon and in CP. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells than that in non-schizophrenic cases. These results suggest that an increase in DAO expression in parts of the brain is involved in aberrant d-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate d-amino acid concentration by modulating the cerebrospinal fluid and may be regarded as a potential therapeutic target for schizophrenia.

Nucling is a stress-inducible protein associated with apoptosomes. The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis. We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well. Here we show that hepatocellular carcinoma (HCC) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout (KO) mice than wild-type (WT) mice. Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males. In the background of Nucling-KO mice, we observed the up-regulation of TNFalpha, spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver. In addition, we observed a decrease in the number of Kupffer cells (KCs) in the KO mice. KCs are important for the hepatic immune system, acting as phagocytes or antigen-presenting cells (APCs). We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha. These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver. We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development.

To clarify the role of thrombin in fibroblast growth and the development of pulmonary fibrosis in bleomycin-induced interstitial lung disease, we examined the relationship of thrombin activity to fibroblast growth-stimulating activity (FGA) in bronchoalveolar lavage (BAL) fluid from bleomycin-treated rats. Male Wistar rats were given a single intratracheal injection of bleomycin, BAL was performed 2, 6, and 15 days later, and the BAL fluid was assayed for thrombin activity and FGA. Higher FGA than the control value was detected in the BAL fluid from rats on day 6 after bleomycin administration. In bleomycin-treated rats, thrombin activity in the BAL fluid was significantly elevated on day 2 and maximal on day 6. The FGA of the BAL fluid from bleomycin-treated rats on day 6 was significantly decreased by its treatment with various thrombin inhibitors, such as alpha 1-protease inhibitor, antithrombin III, hirudin, and MD-805. In our assay, purified rat thrombin also showed FGA in vitro, and its FGA was inhibited by the same concentrations of these thrombin inhibitors as those inhibiting the activity in the BAL fluid. On ammonium sulfate fractionation, most of the thrombin activity was recovered in the fraction of 35 to 50% saturation in which most of the FGA was detected. These results suggest that the FGA of the BAL fluid from bleomycin-treated rats was at least partly due to thrombin is responsible, at least in part, for fibroblast growth and pulmonary fibrosis in bleomycin-induced interstitial lung disease.

A novel intrahepatic biliary cell culture/in vivo transplantation system has been developed with an essentially pure population of bile ductular epithelial cells isolated from rat liver 6-12 weeks after bile duct ligation. In primary culture, these cells retain staining strongly for gamma-glutamyltranspeptidase and glutathione S-transferase P. The cytoplasm of cultured bile ductular cells reacts with an anti-laminin antibody, but loses immunoreactivity with a monoclonal anti-cytokeratin 19 antibody. Semiconservative DNA synthesis in the cultured cells was dependent upon the continued presence of 10% fetal calf serum in the medium. Replicating bile ductular cells could be subcultured for a finite number of passages. In addition, freshly isolated bile ductular epithelial cells gave rise to well differentiated bile ductular structures when transplanted into the interscapular fat pads of syngeneic recipient rats.

A specific antibody against purified human liver guanase was raised in rabbits. The antiserum formed a single precipitin line with human liver extracts, and completely inhibited the activity of the enzyme derived from human liver and kidney. Immunoblotting showed that the antibody bound only to the one protein band of liver and kidney guanase activity. In immunohistochemical studies, the DAB (3, 3′-diaminobenzidine tetrahydrochloride)-reaction with this antibody was positive in the same locations as the histochemical guanase reaction. Moreover, biochemical data of enzymic activity in nephron segments of the rat indicated that guanase activity was located in the proximal tubules. Thus, the DAB reaction appeared to show the location of guanase itself. This immunohistochemical procedure for detection of guanase should useful in clinical studies on this enzyme.

Ovarian fibromatosis is a rare benign nonneoplastic condition with ovarian enlargement in young women and characterized by a proliferation of collagen-producing spindle cells surrounding normal ovarian structures. We reported magnetic resonance findings of a case that the affected ovarian parenchyma with follicles was surrounded by very low intense thick fibrous tissue on T2-weighted images such as "black garland" around the ovary. The magnetic resonance findings well reflected the pathological feature of the disease and may be diagnostic.

Recent advances made in the isolation, culture, and transplantation of defined populations of intrahepatic biliary epithelial cells and oval cells have permitted direct analysis of the functions, growth properties, and differentiation potential of these respective cell types in their untransformed or transformed states. This review provides a current and comprehensive examination of the various approaches that have been taken to isolate and culture intrahepatic biliary epithelial cells from normal and cholestatic liver and oval cells from preneoplastic liver. Emphasis is placed on comparing the phenotypic features and growth properties of these various biliary cell types in vitro as well as on describing their transplantation into ectopic tissue sites. In addition, the oval cell is evaluated in terms of its potential role as a 'facultative stem cell' during hepatocarcinogenesis.

The present study evaluated correlations between preoperative bile juice cytology and mucin expression of surgical specimens in biliary tract carcinoma. Twenty-five patients with biliary tract carcinoma surgically treated at our hospital, whose bile juice cytology had been evaluated before operation, were allocated to this study. Biliary cytology was classified into three categories based on the Papanicolaou classification. Immunohisto- chemical staining of tissues was performed using MUC1 and MUC2 monoclonal antibodies. Lesions showing MUC1 expression of++ or higher and MUC2 expression of - were classified as Group A, and the remaining lesions as Group B. According to the epithelial site, pre- operative cytology was highly correlated in Group A, while it was negative in Group B (p

We report herein a case of renal capsular hemangiosarcoma. A 68-year-old man was admitted to our hospital for treatment of a retroperitoneal tumor identified incidentally on abdominal computed tomography (CT) for follow-up of superficial bladder tumor. The tumor was about 7cm in diameter, positioned between the right kidney and the liver. Right nephrectomy was performed under a diagnosis of renal capsular tumor. Pathological diagnosis was hemangiosarcoma and positive surgical margins were suspected. Radiotherapy was performed postoperatively to a total dose of 50 Gy. Hemangiosarcoma frequently occurs in the skin, but is rare in the retroperitoneal cavity. Neither metastasis nor recurrence has been seen as of 19 months postoperatively.

Aims: To determine whether the presence of large intrahepatic blood vessels (≥3 mm) affect radiofrequency (RF)-induced coagulation necrosis, the gross and histological characteristics of RF-ablated areas proximal to or around vessels were examined in normal pig livers. Methods: An RF ablation treatment using a two-stepwise extension technique produced 12 lesions: six contained vessels (Group A), and the other six were localized around vessels (Group B). Results: Gross examination revealed that the longest and shortest diameters of the ablated lesions were significantly larger in Group B than in Group A. In Group A, patent vessels contiguous to the lesion were present in a tongue-shaped area, whereas the lesions in Group B were spherical. Staining with nicotinamide adenine dinucleotide diaphorase was negative within the ablated area; but, if vessels were present in the ablated area, the cells around the vessels in an opposite direction to the ablation were stained blue. Conclusions: Roll-off can be achieved with 100% cellular destruction within a lesion that does not contain large vessels. The ablated area was decreased in lesions that contained large vessels, suggesting that the presence of large vessels in the ablated area further increases the cooling effect and may require repeated RF ablation treatment to achieve complete coagulation necrosis.

Nucling is a novel apoptosis-associated molecule, which is involved with cytochrome c /Apaf-1/caspase-9 apoptosome induction following pro-apoptotic stress. In the present study, we show first that Nucling is able to interact with galectin-3. Galectin-3 is known to participate in many biological processes, including apoptotic cell death. Nucling was found to down-regulate the expression level of galectin-3 mRNA/protein. Nucling-deficient cells, in which galectin-3 expression is up-regulated, appeared to be resistant to some forms of pro-apoptotic stress as compared with wild-type cells. In addition, the preputial gland from Nucling-deficient mice expressed a significant level of galectin-3 and exhibited a high incidence of inflammatory lesions, indicating that Nucling plays a crucial role in the homoeostasis of this gland by interacting with the galectin-3 molecule and regulating the expression level of galectin-3. Up-regulation of galectin-3 was also observed in the heart, kidney, lung, testis and ovary of the Nucling-deficient mice. In order to confirm the functional interaction between Nucling and galectin-3, a well-documented candidate for the mediator of galectin-3 expression, NF-kappaB (nuclear factor kappaB), was investigated as well. Nucling was shown to interfere with NF-kappaB activation via the nuclear translocation process of NF-kappaB/p65, thus inhibiting the expression of galectin-3. Taken together, we propose that Nucling mediates apoptosis by interacting and inhibiting expression of galectin-3.

The authors present a rare case of celiac artery aneurysm treated by aneurysmectomy and vascular reconstruction, and they review the past literature. A 57-year-old man was referred to their hospital with a complaint of epigastric discomfort. Abdominal echography, 3-dimensional computed tomography, and selective angiography showed a sole celiac artery aneurysm. At operation, the origin of the celiac artery and adjacent aorta was exposed through a midline transperitoneal approach alone. A 25 x 20 x 25 mm fusiform aneurysm of the celiac artery was found 5 mm distal from its origin. Aneurysmectomy and in situ aortoceliac artery reanastomosis was performed buttressed with a doughnut-shaped Teflon felt under the partial clamp of the abdominal aorta. The left gastric artery arising from the aneurysm was ligated. Postoperative angiography showed good patency of the splenic and common hepatic arteries. He had an uneventful postoperative course with no aggravation of the liver function and was discharged 11 days after operation. Pathological examination of the aneurysmal wall revealed medial degeneration with a tear of the internal elastic lamina and intimal edema. In situ aortoceliac artery reanastomosis after aneurysmectomy, as was done in this case, has not been previously documented in the past literature.

Glycogen-rich carcinoma is a rare special histologic subtype of breast cancer and its incidence is estimated to be 1.4% in breast malignancies. However, its precise characteristics in cytological specimens have not yet been fully clarified.Fifty-nine-year-old and 53-year-old women underwent fine-needle aspiration biopsy cytology (FNABC) of a breast tumor, confirming malignancy. A mastectomy with axillary dissection was performed. Cytologically, a moderate amount of eosinophilic, finely granular cytoplasm was seen in the majority of the tumor cells, however, foamy and vacuolated cytoplasm was noted in some tumor cells. Histologically, the tumor cells of both cases had clear and granular cytoplasm, which showed a positive reaction with periodic acid-Schiff, eliminated by diastase.While clear cytoplasm in the tumor cells in the FNABC seemed to be a pivotal cytological characteristic of glycogen-rich carcinoma, it may not be a major component of cytological specimens. Routine periodic acid-Schiff staining may be required to diagnose glycogen-rich carcinoma in cytological methods.

Although metastases of malignant tumors to the jaws are not unusual, metastases to the gingival soft tissues are relatively rare.The clinicopathologic features of a metastatic tumor in the mandibular gingiva originating from lung cancer are described. The patient, a 61-year-old man, was admitted to the hospital with complaints of bloody sputum and chest pain while coughing. The patient's chest radiograph showed an abnormal mass in the left upper lobe. After admission, the patient noticed a swelling of the right mandibular gingiva. Histological and immunohistochemical analysis for tumors of the gingiva and the lung were performed.Radiographic examination did not indicate involvement of the underlying bone. The histopathological findings showed that the gingival tumor consisted of a large cell carcinoma, and the mass of the upper lobe displayed the same histology as that found in the gingiva. Immunohistochemical investigation of the gingival tumor revealed similar results to those found in the mass of the lung. Based on the clinicopathologic findings, this case was diagnosed as primary lung cancer with the gingival tumor deemed metastatic. Multiple metastases were found in areas other than the oral cavity; radiation and chemotherapy for the gingival tumor were performed due to persistent bleeding and pain.The resemblance of this gingival mass to an inflammatory lesion demonstrates the need for a detailed examination. This case also emphasizes the need to evaluate positive treatment needed to relieve complications in the mouth, even if the prognosis of the primary tumors remains unfavorable.

We report an 18-year-old male patient who developed chronic hepatitis C after blood transfusion and had testicular dysfunction after irradiation for a testicular relapse of childhood acute lymphocytic leukemia after cessation of maintenance therapy, and the initiation of testosterone replacement therapy at puberty. Concomitant administration of estradiol resulted in a reduction in serum alanine aminotransferase and ferritin levels and hepatic iron concentration and staining after 2 years of estrogen therapy, although interferon therapy was withdrawn because of adverse effects. This observation suggests that endogenous estradiol may play a beneficial role in male patients with chronic hepatitis C.

Background: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with α-interferon (IFN-α) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. Methods and Results: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. Conclusions: These findings suggest that IFN-α treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C.

We present three cases of so-called mesothelial/monocytic incidental cardiac excrescences (MICE) of the heart and a brief review of related literature. Case 1 was a 51-year-old woman who underwent mitral- and aortic-valve replacement. A tissue sample was submitted as a thrombus attached to the left atrial endocardium. Case 2 was a 69-year-old woman who underwent mitral-valve replacement. The sample was incidentally obtained as whitish clot-like fragments, but its exact origin was not known. Case 3 was a 68-year-old woman who underwent mitral-valve replacement for suspected infective endocarditis. The sample adherent to the pericardium was removed after valvular surgery. Histologically, these lesions were composed of a mixture of plump histiocytoid cells, a papillary arrangement of cuboidal cells, various sized vacuoles, and fibrin. The nests of cuboidal cells resembled cancer cells but showed features of mesothelial cells and no proliferative activity, immunohistochemically or ultrastructurally. In all cases, a suction tube placed in the left atrium was occasionally used to remove overflowing intrapericardial fluid during the surgery. The tip of the suction tube was covered with spiral wire, which is likely to transfer the stripped pericardial mesothelial cells to the left atrium. The significance of MICE is their possibility of being misdiagnosed as metastatic carcinoma by pathologists and a risk of arterial embolization by mesothelial debris clinically.

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.

We report computed tomographic and magnetic resonance findings of an ovarian malignant Brenner tumor with transition from benign to malignant components. The tumor was demonstrated as a cystic mass with solid mural components. The benign component contained dense calcifications on computed tomography and showed very low intensity on T2-weighted images, whereas the malignant component showed high intensity. The admixture of 2 components may well reflect the pathological feature and may be a diagnostic clue to malignant Brenner tumor.

The carcinogenicity of a mixture of capsaicinoids (64.5% capsaicin and 32.6% dihydrocapsaicin) was examined in B6C3F1 mice. In a 13-week toxicity study, renal toxicity was observed in 1% capsaicinoid-treated males. Next, groups of 50 mice of each sex were given 0, 0.025, 0.083 or 0.25% capsaicinoids in powdered diet for 79 weeks and killed in week 83. Food intake was reduced in mice of all capsaicinoid-treated groups, especially females, because of the pungency of capsaicinoids, and inhibition of body weight gain was apparent in females. The numbers of tumour-bearing females in the high-dose groups were significantly lower than that in the controls, and the incidences of hepatocellular neoplasms in both sexes were negatively correlated with the dose of capsaicinoids (Cochran-Armitage trend test). Renal cell adenomas developed in one mouse each of 0.025 and 0.25% capsaicinoid-treated males. The incidences of other tumours were similar in the treated and control groups. Thus, the present study indicated that a mixture of capsaicinoids is not carcinogenic in B6C3F1 mice.

A case of adenosarcoma arising from the uterine cervix of a 55-year-old female who complained of vaginal discharge is reported. A polyp, 6 x 2 x 1.5 cm in size, identified in the cervical canal was clinically diagnosed as benign cervical polyp and resected. Histologically, the polyp was composed of benign epithelial components and sarcomatous stroma wherein periglandular hypercellularity and some mitoses including atypical ones were noted. Immunohistochemically, stromal cells were positive for muscle-type actins, desmin and estrogen receptor. Adenosarcoma is a rare, biphasic tumor of the uterus and usually presents as a polypoid mass in the endometrial cavity. When they arise from the cervix, adenosarcomas may be confused with benign cervical polyps clinically and pathologically. As the former often recurs, microscopic differentiation is crucial for further treatment.

A 53-year-old female suffering from renal stones and hypercalcaemia was diagnosed as having primary hyperparathyroidism caused by hyperplasia of the parathyroid glands. She underwent total parathyroidectomy and implantation of parathyroid tissue. After one year, she underwent surgery for a jaw tumour. The pathological findings indicated it to be a cementifying fibroma. Jackson et al. (1990) reported the familial association of hyperparathyroidism with jaw tumours, and they suggested that this condition represents a new clinical syndrome. We believe that our case belongs to this syndrome.

Nasopharyngeal teratomas are uncommon neoplasms found in neonates. A rare case of a teratoma arising from the nasal septum of a newborn associated with an acardiac amorphous twin is described. Antenatal ultrasonography suggested a fetal anomaly, for which a cesarean section was performed. Immediately after birth the tumor was excised, thereby eliminating life-threatening respiratory distress. The postoperative course was uneventful.

Hepatic involvement of cytomegalovirus (CMV) was studied in 15 autopsy cases with disseminated or solitary CMV infection. Formalin-fixed, paraffin-embedded tissue sections were examined by immunohistochemistry (IHC) using a monoclonal antibody against early and late CMV antigens, and by in situ hybridization (ISH) using biotinylated CMV DNA probes. Three cases showed cytomegalic cells in liver sections by conventional staining, five showed hybridization with CMV DNA probes and seven showed reaction with the monoclonal antibody in the liver. CMV infection was detected not only in cytomegalic cells but also in many non-cytomegalic cells by IHC and ISH, proving these techniques to be superior to routine histological examination. The inflammatory reaction in the liver was not prominent. The reason for the weak inflammatory response in the liver of our present cases, and the possible availability of IHC and ISH for analysis of liver biopsy and bronchoalveolar lavage specimens from immunocompromised hosts were discussed. Acta Pathol Jpn 41: 668–672, 1991.

For assessment of the carcinogenic potential and the mutagenicity of dipyrone, an antipyretic anodyne, -[(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl) methylamino]-methanesulfonic acid sodium salt monohydrate, three experiments were conducted using dipyrone A produced in Japan and/or dipyrone B obtained from the Federal Republic of Germany. (i) Carcinogenic potential of dipyrone A for rat liver: 8 week old male F344 rats were pretreated with 0.01% diethylnitrosamine (DEN) in drinking water for 2 weeks and, after 1 week of resting, administered 0.4% dipyrone in drinking water, 5 days a week, for 72 weeks. After an 8 week recovery period, all surviving rats were killed at 83 weeks. Hepatocellular carcinomas developed at a higher incidence in the DEN + dipyrone group (18 of 29 rats, 62%) than in the DEN alone group (9 of 29 rats, 31%), the difference being statistically significant (P less than 0.05). No carcinogenic activity of dipyrone was demonstrated in the groups given 0.4% dipyrone for 72 weeks or 0.4% dipyrone for 25 weeks, followed by 0.05% phenobarbital (PB) for 50 weeks. However, glutathione S-transferase P positive (GST-P+) preneoplastic hepatic foci in these groups were observed at a higher incidence than in the untreated control group (P less than 0.01). (ii) Effect of dipyrone A and dipyrone B on induction of DEN-initiated GST-P+ hepatic foci in a medium-term bioassay system: 0.4% dipyrone A in drinking water and 0.57% dipyrone A or dipyrone B in powdered diet after DEN initiation had similar enhancing effects on the development of GST-P+ foci (P less than 0.001). (iii) The Ames mutation test in Salmonella: both dipyrone A and dipyrone B proved weakly mutagenic for strain TA100 in the presence or absence of S9 fraction.