bluuebunny/crossref_metadata_2025 huggingface dataset:
Amyloid Enhancing Factor (AEF) Isolation and Biochemical and Pathological Characteristics
Authors: Yokota Tadaaki , Takahashi Mutsuo , Ishihara Tokuhiro , Yamashita Yoshimi , Gondo Toshikazu , Kawamura Shunji , Hoshii Yoshinobu , Koga Mayumi , Iwata Takako , Uchino Fumiya
Published: December 2008

Neutrophils and spleens were prepared from mice after treatment to induce amyloid deposition. The deposition of amyloid was accelerated in normal recipients by intravenous injection of more than 2x104 neutrophils, and intraperitoneal injection of supernatants obtained by homogenization and centrifugation of the neutrophils and spleens. The supernatants were subjected individually to DEAE ion–exchange chromatography. Amyloid enhancing factor (AEF) activity was present in peaks eluted at an NaCl concentration of 0.17 M. The fractions containing AEF were subjected to high‐performance liquid chromatography (HPLC), and AEF was eluted at a position corresponding to about 15 KDa. Purified AEF was analyzed by amino acid sequencing and gas chromatography. The N‐terminal amino acid was blocked, and AEF contained some saccharides including glucose, mannose, galactosamine and sialic acid, and an undefined substance (probably derived from certain proteins). Immunoelectron microscopy by the preembedding method using an anti‐AEF antiserum demonstrated that the cytosol, but not primary and specific granules in neutrophils from the spleen of amyloid‐laden mice, reacted with the antiserum. These findings suggest that AEF is a glycoprotein associated with neutrophils.
HLA‐DR Expression on M Cells Overlying Peyer's Patches is a Common Feature of Human Small Intestine
Authors: Nagura Hiroshi , Ohtani Haruo , Masuda Takayuki , Kimura Mitsuo , Nakamura Shiro
Published: December 2008

The expression of major histocompatibility complex (MHC) class II (HLA‐DR) antigens on M cells within follicle‐associated epithelial cells (FAE) covering Peyer's patches was analyzed immunohistochemically. HLA‐DR antigens were strongly expressed on M cells and cells with dendritic morphology, whereas other FAE covering Peyer's patches showed weak, but definite staining. Dendritic cells were also positive for S‐100 protein and IL‐1. These findings suggest that M cells as well as dendritic cells within FAE form an antigen‐presenting cell system and contribute to the first information releaser for the mucosal immune system.
Von Recklinghausen's Disease Associated with Somatostatin‐rich Duodenal Carcinoid (Somatostatinoma), Medullary Thyroid Carcinoma and Diffuse Adrenal Medullary Hyperplasia
Authors: Yoshida Aichi , Hatanaka Shingo , Ohi Yasuyo , Umekita Yoshihisa , Yoshida Hiroki
Published: December 2008

This report describes the concomitant occurrence of a somatostatin‐rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50‐year‐old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero‐cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma‐bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type Ila or IIb.
Apocrine Adenocarcinoma of the Bilateral Axillae
Authors: Yoshida Aichi , Kodama Yoshifumi , Hatanaka Shingo , Takasaki Takashi , Kuriwaki Kazumi , Yoshida Hiroki
Published: December 2008

A case of apocrine adenocarcinoma arising in the bilateral axillae is reported. The patient was an 88 year old Japanese male who complained of a mass lesion and puslike discharge in the right axilla. Another mass was also noticed in the left axilla. No other neoplastic lesion was found in other sites of the body. The histologic appearances of the bilateral axillary tumors were almost identical. Both were adenocarcinoma with varying degrees of differentiation, composed of glands and nests of atypical epithelial cells with abundant eosinophilic cytoplasm. Some neoplastic cells exhibited cytoplasmic projections on their apical surface. Foci of in situ carcinoma were observed within the neoplastic tissue in the bilateral axillae. The neoplastic cells were immunohistochemically positive for epithelial membrane antigen (EMA) and gross cystic disease fluid protein (GCDFP‐15), but negative for carcinoembryonic antigen (CEA). On the basis of their histologic and immunohistochemical features and distinctive location, the tumors were diagnosed as apocrine adenocarcinoma. Acta Pathol Jpn 41: 927‐932, 1991.
Pathogenesis of HIV Encephalitis
Authors: Wiley Clayton A. , Schrier Rachel D. , Morey Mitchel , Achim Christian , Venable J. Clark , Nelson Jay A.
Published: December 2008

A wide spectrum of infectious agents attack the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients. Human immunodeficiency virus (HIV) itself, infects the CNS of a subgroup of these patients. The mechanism behind why HIV enters the CNS is unclear. We have observed an interesting association between HIV and opportunistic viral infections that may explain why HIV enters the brain. Infection of the CNS by opportunistic agents results in recruitment of latently HIV infected monocytes. Upon differentiation into macrophages these cells produce abundant HIV. Latent HIV‐infection of monocytes/macrophages provides a unique opportunity for cooperativity between opportunistic infections and HIV in mediating CNS damage.
HIV Encephalopathy: Incidence, Definition and Pathogenesis
Authors: Kleihues Paul , Leib Stephen L , Strittmatter Christian , Wiestler Otmar D. , Lang Walter
Published: December 2008

The incidence of HIV encephalopathies was determined in an ongoing consecutive autopsy study. Among 345 patients who died from AIDS in Switzerland during 1981–1990, 68 (19%) showed morphological evidence of HIV encephalopathy. Two major histopathological manifestations were observed. Progressive diffuse leukoencephalo‐pathy (PDL) was present in 33 cases and is characterized by a diffuse loss of myelin staining in the deep white matter of the cerebral and cerebellar hemispheres, with scattered multinucleated giant cells but little or no inflammatory reaction. Multinucleated giant cell encephalitis (MGCE) was diagnosed in 32 cases; it's hallmarks are accumulations of multinucleated giant cells with prominent inflammatory reaction and focal necroses. In 3 patients both types of lesions overlapped. Brain tissue from 27 patients was analyzed for the presence of HIV gag sequences using the polymerase chain reaction (PCR) with primers encoding a 109 base pair segment of the viral gene. Amplification succeeded in all patients with clinical and histopathological evidence for HIV encephalopathy but was absent in AIDS patients with opportunistic bacterial, parasitic and/or viral infections. Potential mechanisms by which HIV exerts it's adverse effects on the human CNS are discussed.
Lobular Involvement in Human Breast Carcinoma
Authors: Ishige Hideo , Komatsu Teisuke , Kondo Yoichiro , Sugano Isamu , Horinaka Etsuo , Okui Katsuji
Published: December 2008

One hundred twenty‐nine cases of breast carcinoma were examined in order to clarify the occurrence of lobular involvement with regard to stromal invasion. Lobular involvement was clearly recognized in 56 cases (43%) having discernible portions of intraductal carcinoma components. The process of lobular involvement was first recognizable as an extension of a few carcinoma cells from intralobular ducts into the acinar lumina. Progressive accumulation of the carcinoma cells resulted in marked swelling and distortion of the involved lobules. During the process, perilobular myoepithelial cells (actin positive cells) were stretched and disappeared. Subsequently, breaks in the basement membranes were also observed, resulting in stromal invasion of carcinoma cells. The lobular involvement was classified into common and round varieties, possibly reflecting different growth activities of the carcinoma cells. The stromal invasion was initiated by peripheral budding or focal necrosis of the involved lobules. The latter pattern was often observed in comedo carcinoma. It was thus revealed that in breast carcinomas the terminal ductal‐lobular units are quite often involved and can become sites of extraductal invasion.
Immunohistochemical Demonstration of Epidermal Growth Factor Receptor and Ceruloplasmin in Thyroid Diseases
Authors: Song Bao‐ping
Published: December 2008

The expression of epidermal growth factor receptors (EGFR) and ceruloplasmin (CP) in thyroid diseases was investigated by immunohistochemical methods, and the results were compared with the expression of thyroglobulin (TG). Eighty eight surgical specimens of thyroid diseases, including follicular carcinoma (7 cases), papillary carcinoma (20 cases), follicular adenoma (29 cases), adenomatous goiter (10 cases), diffuse hyperplasia (20 cases) and chronic thyroiditis (2 cases), were studied. All cases of follicular carcinoma and 18 cases (90%) of papillary carcinoma expressed the EGFR immunoreaction in the cytoplasm with a moderate to strong staining intensity. A weak immunoreaction for EGFR was noted in some benign thyroid diseases. CP showed various degrees of positivity in all cases of follicular carcinoma and 19 cases (95%) of papillary carcinoma. The benign thyroid lesions were consistently negative for this antigen, not counting one case of Hiirthle cell adenoma. There was a positive correlation between EGFR and CP immunostaining intensity in thyroid carcinomas, representing higher expression of EGFR accompanied by a stronger staining intensity of CP. Except for two cases of papillary carcinoma, all cases showed immunoreaction for TG. The results indicate the enhanced expression of EGFR and CP in thyroid carcinomas. EGFR and CP thus appear to be valuable tools for differential diagnosis between benign and malignant thyroid neoplasms.
Minute Carcinoid Tumor of the Gallbladder
Authors: Mochizuki Makoto
Published: December 2008

A minute carcinoid tumor of the gallbladder is reported. The tumor was incidentally identified in a 77 year‐old Japanese man with cholecystolithiasis, hepatocellular carcinoma and sigmoid colon carcinoma. The tumor formed a 5 mm sized sessile polyp at the neck of the gallbladder. The tumor cells, which were argyrophilic and non argentaffinic, belonged to the foregut‐type. Immunohisto‐chemically, they were positive for neuron‐specific enolase (NSE) and somatostatin.
Immunohistochemical Observation of Recovery of the Periarteriolar Lymphoid Sheath, Lymph Follicle and Marginal Zone in the 60Co‐irradiated Spleen of Rats
Authors: Satoh Takashi
Published: December 2008

After 60Co irradiation of rat spleen, the most severe damage was found initially in the lymph follicles (LFs); lymphocytes were decreased in number in the periarteriolar lymphoid sheath (PALS), and almost completely depleted in the marginal zone (MZ). Recovery was observed first in the PALS, followed by the LFs, and finally the MZ. From the results of immunohistochemistry, the process of recovery was assumed to involve migration of T and B lymphocytes along the arterioles from the area surrounding the terminal arteriole at the end of the PALS into the central part of the PALS and into the LF. Peripheral blood lgM+, IgD− B lymphocytes, known to be MZ precursor cells, flowed from the follicular artery to settle in the MZ. Furthermore, recovery of the PALS prior to the LFs was suggested to be essential for lymphocyte migration to the LFs. Acta Pathol Jpn 41: 581‐589, 1991.
Transferrin Receptors and Selective Iron Deposition in Pancreatic B Cells of Iron‐overloaded Rats
Authors: Lu Jian‐ping , Hayashi Keiki , Okada Shigeru , Awai Michiyasu
Published: December 2008

Iron overload was produced in Wistar rats by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+‐NTA) for one to six months. Pancreatic tissues from these iron‐overloaded rats and untreated controls were examined for insulin (for B cells), glucagon (for A cells), transferrin receptor (TfR), transferrin (Tf) and ferritin (Ft) using immunohistochemical methods, and for iron by histochemical Berlin blue staining. In the islets of iron‐overloaded rats, increased Ft staining appeared prior to deposition of Berlin blue‐stainable iron, and the staining intensity of Ft and iron was stronger in B cells than in A cells. In the islets of untreated control rats, the staining intensity of TfR was stronger in B cells than in A cells. TfR staining of the islets was weaker in iron‐overloaded rats than in the controls. These findings suggest that 1) iron uptake by islet cells in vivo is regulated and mediated by TfR, 2) intracytoplasmic Ft transforms into stainable iron in iron‐overloaded rats, and 3) predominance of TfR expression in B cells may result in selective deposition of iron and predispose B cells to damage and diabetes mellitus in iron‐overloaded rats. Acta Pathol Jpn 41: 647–652, 1991.
Atypical Primitive Neuroectodermal Tumors Comparative Light and Electron Microscopic and Immunohistochemical Studies on Peripheral Neuroepitheliomas and Ewing's Sarcomas
Authors: Hasegawa Tadashi , Hirose Takanori , Kudo Eiji , Hizawa Kazuo , Yamawaki Shinya , Ishii Seiichi
Published: December 2008

Recently, primitive neuroectodermal tumors (PNETs) have been shown to cover a wide spectrum of small round cell sarcomas, probably including some Ewing's sarcomas (ESs) and extraskeletal Ewing's sarcomas (EESs), in addition to classical peripheral neuroepitheliomas (PNs). In studies of small cell sarcomas, we found a group of undifferentiated tumors resembling PNETs with some features of neuroectodermal differentiation, but possessing areas of relatively large, pleomorphic cells. To clarify the nature of these tumors and their relationship to PNETs, we examined the variety of histological, immunohistochemical and ultra‐structural features of 11 small cell sarcomas. Five of these tumors were composed of uniform, small round cells and were classified as PNs because of the presence of definite Homer‐Wright rosettes and fibrillary processes. The presence of well developed neurite like processes containing neurosecretory granules and immunore‐activities for various neural markers suggested that these PNs showed more advanced neuronal differentiation. Two tumors, with the classical features of ES, showed no ultrastructural evidence of neuronal differentiation, although only gamma gamma neuron specific enolase (NSE) positivity was detected. Four undifferentiatied tumors with atypical features, included in this study as an atypical PNET group, showed certain neuroectodermal characteristics, such as ganglion cell differentiation, perivascular pseudorosettes, and gamma gamma NSE reactivity. It is concluded from this study that PNETs may include small round cell tumors showing different degrees of neuroectodermal differentiation and some histological variations. Acta Pathol Jpn 41: 444–454, 1991.
Cardiac Tamponade Due to Rupture of a Subepicardial Aneurysm Following Myocardial Infarction
Authors: Imakita Masami , Kurishima Setsuko , Yutani Chikao , Ishibashi‐Ueda Hatsue , Saeki Kazunori , Haze Kazuo
Published: December 2008

A 71 year old male died of cardiac tamponade due to cardiac rupture 22 days after onset of acute myocardial infarction. Autopsy revealed rupture of an unusual ventricular aneurysm characterized by abrupt interruption of the myocardium, a narrow neck, a thin fibrous outer wall partially showing myocardial fibers, and lack of adhesion between the epicardium and pericardium. A review of the literature revealed that 11 among 32 autopsy cases of false aneurysm showed a similar morphology to the present case, these being classifiable as subepicardial aneurysm. Acta Pathol Jpn 41: 52 58, 1991.
Pulmonary Mucormycosis with Fatal Massive Hemoptysis
Authors: Harada Miki , Manabe Toshiaki , Yamashita Koshi , Okamoto Naoto
Published: December 2008

A case of pulmonary mucormycosis in a 57 year old woman with acute promyelocytic leukemia (APL) who died of massive hemoptysis is reported. Chest radiography revealed changes that began with a small focal infiltration and progressed to a large round nodule with cavity formation. Postmortem examination showed the nodule to be composed mainly of infarcted lung tissue with saprophytic growth of Mucor. An adjacent proximal branch of the left pulmonary artery was thrombosed with mucoraceous hyphae, and it had ruptured into the cavitary space around the necrotic tissue and then into a conducting bronchus. In general, both fatal massive hemoptysis and cavity formation are rare in pulmonary mucormycosis. In our present case, the histological findings suggested that both phenomena were closely related to the pulmonary infarction caused by Mucor invasion of the pulmonary artery.
Endothelial Fenestration of the Alveolar Capillaries in Interstitial Fibrotic Lung Diseases
Authors: Kawanami Oichi , Matsuda Kiyoshi , Yoneyama Hirohide , Ferrans Victor J , Crystal Ronald G
Published: December 2008

A light and electron microscopy study was performed on endothelial cells of alveolar capillaries in biopsied lung tissues obtained from 28 patients with interstitial fibrotic lung diseases, including idiopathic pulmonary fibrosis, sar‐coidosis, hypersensitivity pneumonitis, chronic eosinophilic pneumonia, collagen vascular diseases and acute interstitial pneumonia. In the relatively early stages of acute interstitial pneumonia, hypersensitivity pneumonitis and other diseases, the cytoplasms of the endothelial cells appeared swollen and electron‐lucent and occasionally showed degeneration and necrosis. Although mitosis was not evident in the endothelium at any disease stage, some capillary endothelial cells showed regeneration. Furthermore, although rarely, they showed obvious phenotypic transformation into diaphragmed fenestrae in some limited segments of fibrotic lungs in the 20 of the 28 patients examined. The frequency of endothelial fenestration seemed to be correlated with the degree of interstitial fibrosis along the alveolar walls. In such fibrotic lung tissues, cuboidal metaplastic cells of bronchiolar origin proliferated on the luminal side. The mechanism of endothelial fenestration in the alveolar capillaries is assumed to be comparable with cuboidal metaplasia of alveolar epithelial cells. The alveolar capillary endothelium is recruited from the bronchiolar capillaries via bronchopul‐monary anastomoses unless endothelial repair occurs in situ. Regenerating endothelial cells move into the alveolar capillary tubes along the remnant sleeves of the basement membrane. New endothelial processes finally display their original fenestrated structure while secreting irregular fragments of basement membrane during implantation in the capillary beds. Acta Pathol Jpn 42: 177– 184, 1992.
Segmental Mediolyic Arteritis: Clinicopathologic Study and Three‐dimensionaI Analysis
Authors: Inayama Yoshiaki , Kitamura Hajime , Kitamura Hitoshi , Tobe Michio , Kanisawa Masayoshi
Published: December 2008

We describe the first recorded case of segmental mediolytic arteritis (SMA) in Japan. A 71‐year‐old Japanese woman developed sudden abdominal pain and went into shock during hospitalization for treatment of valvular heart disease. Laparotomy revealed a ruptured pseudoaneurysm of the left gastric artery. Histological examination of the resected artery revealed multiple extensive areas of the dilated wall where the media had partially or totally disappeared with or without the intima. These features were typical of those described previously for SMA (1, 2). Three dimensional analysis of the arterial lesions revealed that the residual media formed branches and cavities down the long axis of the artery, indicating that the major cause of the medial disappearance was arterial dissection. Three months later, the patient died of sepsis. Autopsy revealed pseudoaneurysm formation at three different locations in the splenic artery. Histologically, these pseudoaneurysms showed destructive changes in the arterial wall similar to those described above, with organization and thrombosis, and were considered to be the end stage lesion of SMA. This case is considered to be the fifth adult case of SMA in the literature and the first one showing chronic changes. Acta Pathol Jpn 42: 201–209, 1992.
Localized Primary Amyloid Tumor of the Thyroid Developing in the Course of Hashimoto's Thyroiditis
Authors: Moriuchi Akira , Yokoyama Shigeo , Kashima Kenji , Andoh Takafumi , Nakayama Iwao , Noguchi Shiro
Published: December 2008

A case of localized primary amyloid tumor of the thyroid gland developing in the course of Hashimoto's thyroiditis was studied using histochemistry, immunohistochemistry and electron microscopy. The patient was diagnosed as having Hashimoto's thyroiditis by histological examination of the thyroid and by the presence of a high titer of serum thyroglobulin and thyroid microsomal antibodies. In addition, the thyroid gland exhibited multiple nodular deposits of amyloid which were resistant to prior incubation with potassium permanganate. The amyloid deposits were surrounded by numerous histiocytes and multinucleated giant cells which contained small amyloid droplets in their cytoplasm. However, no amyloid deposits were observed in the walls of blood vessels. lmmunohistochemistry showed that the amyloid was strongly positive for amyloid P component, IgG and kappa light chains. Ultrastructurally, the amyloid was composed of straight fibrils with a diameter of 7 to 10 nm. Histiocytes extended slender cytoplasmic processes in a radial fashion into amyloid fibrils, which exhibited a highly organized star‐like pattern. This was considered to be an extremely rare case of localized primary amyloidosis of the thyroid, in which IgG, especially kappa light chains (AL), was present as a precursor protein. Acta Pathol Jpn 42: 210–216. 1992.
Comparative Study of IntraneuronaI Polyglucosan Bodies in Brains from Patients with Lafora Disease and Aged Dogs
Authors: Yamanami Sadayoshi , Ishihara Tokuhiro , Takahashi Mutsuo , Uchino Fumiya
Published: December 2008

We compared intraneuronal polyglucosan body (PGB) in brains from two patients diagnosed as having Lafora disease and from 18 aged dogs (age range: 10 to 22 years, various breeds). PGBs appeared as various‐sized spheroids intensely stained with periodic acid Schiff (PAS) in both humans and aged dogs. lmmunohistochemistry with a monoclonal antibody raised against human polyglucosan showed positive staining of the PGBs. Ultrastructurally, PGBs in both humans and aged dogs were composed of fibril‐like structures 4 to 20 nm wide. Electron‐dense material formed the central cores of the fibrils, but was also scattered in their peripheral areas. The fibril‐like structures were intensely stained upon application of the Thiéry procedure. lmmunoelectron microscopy showed that the fibril‐like structures were specifically labeled with gold particles. The histological, immunohistochemical and ultrastructural features of the PGBs in humans and aged dogs were quite similar. Acta Pathol Jpn 42: 787–792, 1992.
An Autopsy Case of lnvasive Pituitary Adenoma (Prolactinoma) with Rapid Fatal Clinical Course Due to Streptococcal Meningitis
Authors: Onoda Noboru , Kamezu Yutaka , Takagi Shigeharu , Shinohara Yukito , Osamura R. Yoshiyuki
Published: December 2008

A 44‐year‐old male suffered epistaxis and headache of sudden onset and was diagnosed as having suppurative meningitis due to streptococci. Four days after the onset of symptoms, he died despite treatment with antibiotics. Destruction and ballooning of the sella turcica was revealed by a plain head X‐ray examination during the clinical course. At autopsy, a massive tumorous lesion extended from the ballooned sella turcica to the paranasal cavities, nasopharynx and facial bone, and this had resulted in suppurative meningitis. The tumor was also disseminated to the basal skull. The tumor cells possessed prominent nuclear atypia and were immunohistochemically positive for prolactin. This was diagnosed as a case of pituitary adenoma with markedly invasive pathological findings and a rapid and fatal clinical course. Acta Pathol Jpn 42: 832–836, 1992.
Neonatal Legionnaires’Disease
Authors: Horie Hiroshi , Kawakami Hiroshi , Minoshima Kaori , Kamohara Takashi , Nakamura Tuneo , Kuroki Haruo , Nakamura Akira
Published: December 2008

A neonatal case of legionnaires’disease (LD) is reported. A male neonate was admitted to our hospital with high fever and dyspnea, which had started 5 days after birth, and died due to severe pneumonia at 10 days old. An autopsy revealed small areas of granular consolidation scattered diffusely in the bilateral lungs. Microscopic examination of the lungs showed mainly lobularly distributed pneumonia. Extensive exudation of macrophages and neutrophils was observed in the terminal respiratory tract and alveolar spaces. Warthin‐Starry and Gimenez staining and electron microscopy detected many coccobacilli in the cytoplasm of exudated macrophages and neutrophils. Immunofluorescence staining using antiserum against Legionella pneumophila, serogroup 1, showed a positive reaction. Bacteriological examinations of aspirate from the respiratory tract and autopsied lung tissue confirmed the presence of Legionella pneumophila, serogroup 1. Extrapulmonary LD was not detected. LD usually affects aged or immunocompromised hosts, but there was no evidence of immune deficiency in this case. Pediatric cases of LD have rarely been reported, and a survey of the literature revealed few neonatal cases. The present case may alert neonatologists and other medical personnel to the possibility of neonatal LD infection.
Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern
Authors: Iwai Kazuro , Takemura Tamiko , Kitaici Masanori , Kawabata Yoshinori , Matsui Yasuo
Published: December 2008

Three hundred and twenty autopsy cases of sarcoidosis in Japan were analyzed to determine the pathological changes in the early stage, the mode of progression in each organ and the changes in the final stage of the disease.

The lung and the mediastinal lymph nodes were affected in most of the cases, while the lesions were limited to the lung and intrathoracic nodes in some of the cases. It was suspected that early changes developed in the lung and in the hilar, and then in the mediastinal lymph nodes. The progression of sarcoid granulomas in the lung was classified into three patterns: (i) probably of a disseminated hematogenous nature; (ii) of an interstitial lymphogenous nature; and (iii) of a local expansive nature. These three patterns were observed also in the heart. In the brain, perivascular granuloma formation was a prominent feature. In the other organs in which sarcoid lesions were not malignant nor disseminated and conglomerated, no interstitial patterns were observed.

In chronic cases, repeated dissemination and particularly the interstitial spread of granulomatous changes led to a prominent interstitial fibrosis and dysfunction of the organs, finally resulting in death of the individual. In such longstanding cases, the mediastinal nodes deteriorated by hyalinous degeneration of the granulomas, and many active granulomas were formed in the intra‐abdominal or body surface lymph nodes. These lymph nodes were likely to continue supplying sensitized lymphocytes to the whole body. A persistence of active change in the lymph nodes and the lymphogenous spread of granulomas in organs would appear to be key factors in the prognosis of sarcoidosis.
Morphological and biological changes of a hepatocellular carcinoma cell line cultured in a three‐dimensional matrix of collagen
Authors: Haramaki Makoto
Published: December 2008

A human hepatocellular carcinoma (HCC) cell line, KIM‐1, was cultured in three different concentrations (0.1, 0.2 and 0.3%) of type‐l collagen gel matrix and its morphologic features, growth kinetics and alpha‐fetoprotein and albumin productions were compared with each other or with those of cells growing on a plastic dish. KIM‐1 cells in any concentration of collagen gel matrix formed various sized threedimensional colonies with compact to trabecular cell arrangement. Larger colonies with a more definitive trabecular cell arrangement, resembling the in vivo structure of HCC, tended to form in the collagen gel matrix of a low concentration. The prolongation of doubling time was identified as the collagen concentration in the gel became higher. The cells on a plastic dish proliferated in a monolayered sheet with a shorter doubling time than others. Ultrastructurally, the cells in collagen gel matrix have more distinct cell membranes, junctional complexes and bile canaliculus‐like structures, and less cytoskeletons than those on plastic dishes, similar to those in vivo. The productions of alphafetoprotein per 104 cells and albumin per 1O5 cells were much higher in the collagen gel matrix culture than on a plastic dish in a stationary phase. These data suggest that collagen gel matrix culture is suitable to monitor the morphologic features and protein production of the tumor cells in similar conditions to those in vivo, and that the three‐dimensional presence of an extracellular matrix is important in cellular proliferation and differentiation.
Histogenesis of abnormal elastic fibers in blebs and bullae of patients with spontaneous pneumothorax: Ultrastructural and immunohistochemical studies
Authors: Haraguchi Shuji , Fukuda Yuh
Published: December 2008

Elastic fibers in 15 blebs and 17 bullae with spontaneous pneumothorax were studied by means of electron microscopy and light and electron microscopic immunohistochemistry for elastin and α1‐antitrypsin. Blebs were formed in association with focal organized alveoli, and bullae were formed in association with pulmonary emphysema. Both blebs and bullae had abnormal elastic fibers. Ultrastructurally, abnormal elastic fibers of blebs and bullae consisted of accumulated thick and fine fibers. Accumulated thick elastic fibers showed vacuolar changes and electron‐dense granular deposits, and they were associated with spiraling collagen fibrils. These thick elastic fibers reacted evenly with anti‐elastin antibody and also reacted with anti‐α1‐antitrypsin antibody. They are thought to be degraded elastic fibers. Accumulated fine elastic fibers consisted of bundles of microfibrils and granular amorphous components, and they reacted with anti‐elastin and anti‐α1‐antitrypsin antibody. These fine elastic fibers are thought to be not only newly formed in the process of organization but also degraded. It is suggested that elastic fibers of blebs and bullae are degraded due to an imbalance between elastase and α1‐antitrypsin.
Two cases of recurrent hepatic injury associated with early pregnancy: hCG on hepatocytes is a suspected target antigen for lymphocyte attack
Authors: Miura Katsutoshi , Shirasawa Haruyuki , Nagata Shigeharu , Komoda Fumio , Nakajima Takeyuki , Kanai Koichi
Published: December 2008

Two cases of recurrent hepatic injury which appeared in the first trimester of pregnancy were studied. Case 1 was a 35 year old woman, gravida 4, para 0, who suffered repeatedly from hepatic injury requiring induced abortions. The patient was healthy before the pregnancies and the plasma aminotransferases increased after 8 weeks gestation and promptly returned to normal after the abortions. No fluctuation of aminotransferases was observed in the menstrual cycle. A liver biopsy immediately after abortion showed spotty necrosis of hepatocytes with mononuclear cell infiltration. Most of the infiltrating cells were cytotoxic T cells that were directly in contact with hepatocytes. Numerous lymphocytic infiltrations were also found in the decidua of the uterine curettage material. The patient's lymphocytes showed conspicuous blast transformation in culture with human chorionic gonadotropin (hCG). The hCG was detected in close vicinity to the injured hepatocytes by immunostaining. Case 2 was a 23 year old woman, gravida 2, para 0, who underwent an induced abortion due to hepatic dysfunction in the first pregnancy. Although hepatic dysfunction reappeared from 10 weeks gestation during the second pregnancy, her health gradually improved with conservative therapy and resulted in a full‐term delivery. She lacked allergies to drugs or foods and was healthy when she was not pregnant. These two cases suggest that some hepatotoxic materials appeared transiently in the first trimester. The results of Case 1 suggest strongly that hCG on the hepatocytes was recognized as an antigen and evoked lymphocytic attack.
Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain‐stem in Lewy body disease
Authors: Fukuda Takahiro , Tanaka Junichi , Watabe Kazuhiko , Numoto Robert Tomohiko , Minamitani Motoyuki
Published: December 2008

Three cases of Lewy body disease were investigated in order to compare the morphological and immunohistochemical characteristics of the neuronal inclusions in the cerebral cortex (CC) and brain‐stem (BS). Ultrastructurally, the CC contained intermediate‐sized filaments with variable amounts of granular material and other organelles, whereas the BS consisted of an electron‐dense core and an outer area with radially oriented filaments. The cerebral cortex was immuno‐reactive with antibodies against tyrosine hydroxylase (TH) and tau protein, and differed from BS. In addition, although the CC were antigenically similar to BS in their neurofilament (70, 160 and 200 kDa) and ubiquitin contents, the localization of neurofilament immunoreactivity differed between them, being confined positively to the core of CC, but to the periphery of the BS. Although Lewy bodies (LB) in idiopathic Parkinson's disease are morphologically similar to BS, they have been reported to differ in their immunoreactivity with antibodies against tau. It has been reported that CC differ from LB with regard to immunoreactivity with antibodies against TH and tropomyosin. It is inferred that these inclusions (CC, BS and LB) differ in morphogenesis.
Morphologic variations of dense deposit disease: Light and electron microscopic, immunohistochemical and clinical findings in 10 patients
Authors: Joh Kensuke , Aizawa Shigeo , Matsuyama Norimasa , Yamaguchi Yutaka , Kitajima Takeyuki , Sakai Osamu , Mochizuki Hiroshi , Usui Nobuo , Hamaguchi Kin‐ichi , Mitarai Tetsuya
Published: December 2008

Twenty‐one renal biopsy specimens obtained from 10 patients with dense deposit disease (DDD) were investigated using light microscopy, electron microscopy and immunohistochemistry. The patients included four females and six males aged 6 to 35 years (mean 16.1 years). A morphological diagnosis of DDD was made following the ultrastructural detection of continuous intramembranous dense deposits (CIMDD) in some capillary loops of at least one of the series of the repeated biopsies from each patient. With light microscopy, six patients showed membranoproliferative glomerulonephritis (MPGN). The other four patients showed diffuse proliferative glomerulonephritis (DPGN) with acute lesions showing intraglomerular neutrophilic infiltration, hump formation and endothelial swelling in three and minor glomerular abnormalities in one. Follow‐up biopsies were obtained in six patients. Two patients progressed from DPGN to MPGN within 7 months, whereas three patients with MPGN showed morphologic improvement that featured increased capillary patency and regional disappearance of dense deposits along with the reduction of proteinuria. Dense deposit disease did not always feature typical amorphous and osmiophilic CIMDD spreading across the whole width of the lamina densa. This classical ultrastructural manifestation was mainly found in the patients with histologic non‐MPGN and a linear peripheral pattern of complement component (C3) deposition. The MPGN patients with a granular peripheral pattern of C3 deposition also had CIMDD, but also additionally featured less dense subepithelial deposits superimposed on the CIMDD to produce an appearance simulating membranous transformation. Humplike epimembranous massive dense deposits were also identified in connection with the deposition of immunoglobulin G (IgG), suggesting that immune complex deposition at the glomerular basement membrane occurs in some cases of DDD. Immunoglobulin M (IgM) or complement component 1q (C1q) deposition was often associated with intraglomerular neutrophilic infiltration and endothelial swelling as well as with ultrastructural subendothelial edema. Continuous dense deposits were found not only in the lamina densa but also just beneath the subendothelium in four patients. Thus, the present investigation demonstrated the morphologic variety of DDD in a correlative study of light microscopy, electron microscopy and immunohlstochemistry.
Effects of glomerular macrophages on mesangial cells in rat serum sickness glomerulonephritis: A comparison of histological and co‐culture studies
Authors: Kasai Shinji
Published: December 2008

Effects of glomerular macrophages on mesangial cell proliferation at different stages of experimental serum sickness nephritis (SSN) in the rat were examined using a direct co‐culture system. The results were compared with the manifestations of glomerular tissue at the same points in time during the course of the SSN, especially with regard to glomerular infiltration and glomerular cell proliferation. Macrophages were isolated from the glomeruli at different points in time during the course of the SSN. While the number of glomerular macrophages increased during the sensitization, the proliferating cell nuclear antigen/cyclin positivity of the glomerular tissue was increased after cessation of the antigenic sensitization. The effect of macrophages on mesangial cell proliferation was relatively diminished during the sensitization but was augmented thereafter. Proliferating cells were mostly attached by macrophages, suggesting the importance of the proximity of macrophages for mesangial proliferation. These results suggest that mesangial cell proliferation is largely influenced by macrophage function variability in the glomeruli during the course of SSN.
Sarcomatoid carcinoma of the urinary tract
Authors: Murata Tetsuya , Soga Toshihiko , Tajima Kazuhiro , Saito Kaoru , Komeda Yoshinori , Loshii Sergio Ossamu , Shiraishi Taizo , Sakakura Teruyo , Yatani Ryuichl
Published: December 2008

Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the urinary tract. This tumor had been termed carcinosarcoma because of its carcinomatous and sarcomatous components. There is still some confusion in the terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the latter is now regarded as primarily a malignant epithelial tumor with pseudosarcomatous transformation.

Four cases of sarcomatoid carcinoma arising from the urinary tract are reported. The patients were a 77 year old female, and three males aged 62, 69 and 80 years. All but the eldest patient complained of gross hematurla. Surgical removal was performed in the younger three cases, and an autopsy was done in the remaining case. All the tumors were macroscopically polypoid. Histopathologic examination revealed fasciculated spindle‐cell tumors with myxold stroma or malignant fibrous histiocytoma‐like spindle cell tumors. The epithelial nature was proven in these sarcomatous cells by immunohistochemical andlor electron‐microscopic examinations. Only a small amount of squamous cell carcinoma components was also evident in the latter three cases. Although the younger three patients were alive at 44, 23 and 39 months’follow‐up, respectively, constant careful monitoring Is recommended.
Arthritis and ankylosis in twy mice with hereditary multiple osteochondral lesions: With special reference to calcium deposition
Authors: Sakamoto Michiie , Hosoda Yasuhiro , Kojimahara Kenichi , Yamazaki Touru , Yoshimura Yukio
Published: December 2008

A murine autosomal recessive mutant named twy (tiptoe walking‐Yoshimura) mouse showing multiple osteochondral lesions including ankylosis of the vertebral column and limb joints underwent sequential histopathological analysis of posterior limb joint lesions and intervertebral disc lesions. In the articular cartilage, a decrease in alcian blue‐positive extracellular matrix and the presence of degenerated collagen fibers were found at the age of around 4‐8 weeks. Calcium deposits in the articular cartilage were found at that time and later in the articular space and synovial tissue. Calcium deposits were also found in the intervertebral discs at 4 weeks. Using electron microscopy, some of the crystals were seen inside small vesicles. In both joints, degeneration of, and calcium deposition in, the articular cartilage progressed with age, finally producing bony ankylosis. These histological observations suggest that calcification and degeneration of the articular cartilage are the major factors in the pathogenesis of joint disorders in the twy mouse, and this mutant mouse provides a good model for studying the process and mechanism of osteoarthritic lesions, destructive arthritis and ankylosis.
An immunohistochemical study of Warthin‐Finkeldey cells in measles
Authors: Nozawa Yoshihiro , Ono Nobutaka , Abe Masafumi , Sakuma Hideo , Wakasa Haruki
Published: December 2008

An autopsy case of an 18 month old male infant with measles infection Is reported. An autopsy revealed generalized lym‐phadenopathy, splenomegaly and hyperplastic thymus. Histologically, there were many Warthin‐Finkeldey cells (WFC) in hyperplastic lymphoid tissues. Although viral particles and inclusions were not detected electronmicroscopicaliy, the infection of measles virus was detected in WFC by immunofluorescent technique using anti‐measles antibody. Warthin‐Finkeldey cells were morphologically and immu‐nohistochemically divided into two groups. The first type was WFC appearing in the germinal centers of lymphoid tissue, revealing many large nuclei and B cell markers. The second type was WFC appearing in the interfollicular areas and thymus, showing many small hyperchromatlc nuclei and T cell markers. The data indicate that there might be a morphologic and immunophenotypic heterogeneity in WFC.
Myxoid leiomyoma of the vulva mimicking aggressive angiomyxoma
Authors: Nemoto Taiko , Shinoda Masayuki , Komatsuzaki Kazunori , Hara Takabumi , Kojima Masao , Ogihara Tomonobu
Published: December 2008

A case of vulvar leiomyoma with extensive myxoid change in a 40 year old female is described. The tumor had a unique connection with a non‐degenerative leiomyoma that compressed the rectum and the bladder. Scattered smooth muscle cells in a loose myxoid stroma were immunoreactive for desmin. Fibroblast‐like spindle cells were immunoreactive for vimentin but not for desmin. The initial, although incorrect, pathological diagnosis of the tumor was aggressive angiomyxoma based on the similarity in both clinical and pathological aspects with this more invasive tumor. Myxoid vulvar leiomyoma should also be differentiated from angio‐myoflbroblastoma. The key to the differential diagnosis is the presence of interlacing smooth muscle cells and an awareness of tendency toward myxoid change in vulvar leiomyomas.
Malignant progression of adenomyoepithelial adenosis of the breast
Authors: Tsuda Hitoshi , Mukai Kiyoshi , Fukutomi Takashi , Hirohashi Setsuo
Published: December 2008

A case of breast tumor is described, which consisted of dense and uniform proliferation of ducts and lobules composed of both epithelial and myoepithelial cells and in which multiple foci of adenocarcinoma were observed. The tumor surrounding the carcinoma foci was identified as ‘adenomyoepithelial adenosis’. Adenomyoepithelial adenosis was not monoclonal by clonal analysis, but revealed a relatively high labeling index for proliferating cell nuclear antigen by immunohistochemistry. Although it was still undetermined whether adenomyoepithelial adenosis is a non‐clonal nonneoplastic lesion or a biclonal neoplastic one, the lesion was shown to reveal high proliferative activity in both glandular epithelial and myoepithelial cells and was considered to be prone to progress to obvious carcinoma.
Modulation of cytoskeletal organization of podocytes during the course of aminonucleoside nephrosis in rats
Authors: Kubosawa Hitoshi , Kondo Yoichiro
Published: December 2008

By immunoelectron microscopy the modulation of cytoskeletal organization of podocytes during the course of puromycin aminonucleoside‐induced nephrosis was examined. In control rats, tubulin and vimentin were present, limited to the podocyte cell body and the major processes. Their distribution in the foot processes was virtually negative. Myosin exhibited the same distribution pattern, albeit much more scattered, with no relation to any podocyte organelles or cell structures. Actin was scattered over the fibrillar zones of the cell body and its processes, including the foot processes. In proteinuric rats, loss of foot processes occurred and the glomerular basement membrane was covered by broad cytoplasmic sheets of podocytes, which contained these four subunits of cytoplasmic filaments. Accompanied by the disappearance of proteinuria, the structural organization of the foot processes was completely restored, in which tubulin, vimentin, and myosin were scarcely observed. Our results confirmed that the loss of foot processes is caused by their retraction, and indicated that the specific localization of the podocytic cytoskeleton contributes to the maintenance of the particular cell shape. Its reorganization may account for the structural modification of podocytes.
The developing human biliary system at the porta hepatis level between 29 days and 8 weeks of gestation: A way to understanding biliary atresia. Part 1
Authors: Tan Carolyn E. L. , Moscoso Gonzalo J.
Published: December 2008

The developing biliary system in normal human embryos from 29 days to 8 weeks post‐fertilization was studied. The primitive extrahepatic bile duct that originates from the embryonic hepatic foregut diverticulum is in contact with the hepatic anlage from the start of organogenesis and remains so throughout the gestational ages examined. The primitive extrahepatic bile duct maintains continuity with the ductal plate from which intrahepatic bile ducts are eventually formed. Contrary to long‐held concepts of biliary development, no ‘solid stage’ of entodermal occlusion of the common bile duct lumen was found at any stage of gestation in the material investigated. Therefore, biliary atresia is not caused by incomplete vacuolization of the ‘solid stage’.