bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive oxygen species‐induced molecular damage and its application in pathology
Authors: Toyokuni Shinya
Published: March 2003

Recent studies have clarified that reactive oxygen species (ROS) are involved in a diversity of biological phenomena including radiation damage, carcinogenesis, ischemia– reperfusion injury, diabetes mellitus and neurodegenerative diseases. The breakthrough of these fruitful accomplishments was the discovery of an enzyme, superoxide dismutase, by McCord and Fridovich in 1968. In the 1970s and 80s, biochemists and radiation biologists were attracted by the role of ROS in its irreversible damage to biological molecules. In the 1990s, ROS were further found to be a reversible modulator of protein structure as well, and this led to a recent rapid data accumulation on the association of ROS and transcription factors. At the same time, methods to localize ROS‐induced damage in paraffin‐embedded tissues have been established. This owes to a successful production of antibodies against covalently modified structures specific for ROS‐induced damage. The epitopes include 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal‐modified proteins. The present article reviews histochemical and immunohistochemical methods to localize ROS‐induced damage in tissues and cells, further comments on the association of ROS with transcription factors, and shows a prospective view of ROS‐induced carcinogenesis.
Pathological changes of the spinal cord in centenarians
Authors: Wang Yin , Hashizume Yoshio , Yoshida Mari , Inagaki Toshiaki , Kameyama Takashi
Published: March 2003

In order to study the changes that occur in the spinal cords of the aged, 19 centenarian spinal cords from two men and 17 women (age range, 100–116 years at death; mean, 103 years) were pathologically examined. Cross‐sections at each segmental level of the 19 autopsied spinal cords were examined for histopathological changes. The cross‐sectional area and flattening ratio at the level of the C7 segment were measured. The size of the cords had some negative correlation with age, but the individual variation was considerably large. Among the 19 centenarians, macroscopic anteroposterior flattening appeared in the lower cervical cords in six individuals. In these cases, various degrees of neuron loss were observed in the anterior horn. White matter degeneration appeared frequently, especially in the posterior column. In 12 cases, myelin loss in the fasciculus of Goll at the cervical level was observed. The degeneration of the fasciculus of Goll was considered to be upward wallerian degeneration secondary to posterior root damage at the lumbosacral level. These changes seemed to be produced by disorders in the spinal canal or surrounding tissue, such as cervical spondylosis, degeneration of the intervertebral disk and spinal canal stenosis. Argyrophilic structures such as neurofibrillary tangles and neuropil threads were observed in 16 cases; however, this incidence was less than in the brain. Medial thickening of the anterior spinal artery was found in four cords. Amyloidangiopathy was noted in only one cord. Necrosis and hemorrhage due to vascular disturbance were not found.
Multiple pulmonary leiomyomatous hamartoma with secondary ossification
Authors: Kato Noriko , Endo Yasushi , Tamura Gen , Motoyama Teiichi
Published: March 2003

A 31‐year‐old woman presented with multiple pulmonary leiomyomatous hamartoma (MPLH) with secondary ossification. She had a past history of parosteal osteosarcoma. The pulmonary lesions were composed of spindle‐shaped cells arranged in interlacing fascicles, among which glands or duct‐like spaces were scattered. As some lesions contained bony tissues, it was unclear whether or not the pulmonary lesions were metastases of parosteal osteosarcoma. However, the majority of spindle‐shaped cells were positive for α‐smooth muscle actin, including cells proliferating around the bony tissues. Clonality analysis using a target of human androgen receptor (HUMARA) gene disclosed that the pulmonary nodules were polyclonal. These findings do not indicate that the lesions were metastatic. We would like to emphasize that MPLH can show osseous metaplasia.
Argyrophilic grains in late‐onset Creutzfeldt–Jakob diseased brain
Authors: Kawashima Toshiro , Doh‐ura Katsumi , Iwaki Toru
Published: March 2003

Braak’s argyrophilic grains (ArG) are spindle‐shaped structures originally described in patients with dementia. Herein, a unique case of sporadic Creutzfeldt–Jakob disease (CJD) accompanied by numerous ArG is presented. The pathological picture was typical of CJD based on the findings of routine hematoxylin‐eosin staining. The highest density of ArG was observed throughout the parahippocampal gyrus and the temporal gyri; however, the sector CA1 of the hippocampus showed less ArG. An immunohistochemical analysis for prion protein (PrP) revealed diffuse fine neuropil staining in the cerebral cortex, while the ArG themselves did not demonstrate any immunoreaction for PrP. No correlation was observed between the densities of ArG and either the presence of senile plaques, neurofibrillary tangles or neuropil threads in the present case. To our knowledge, this is the first report of CJD demonstrating numerous ArG.
Tubular seminoma of the testis
Authors: Takeshima Yukio , Sanda Noriaki , Yoneda Kenji , Inai Kouki
Published: March 2003

A case of tubular seminoma in a 33‐year‐old man is reported. The tumor occurred in his right testis, measuring 7 × 6 × 6 cm in size. Microscopically, most of the tumor cells were arranged in solid or hollow tubular patterns. The tumor cells had round nuclei with vesicular chromatin and clear or granular cytoplasm, characteristic features of seminoma cells. A classic seminoma component and intratubular atypical germ cells occupying approximately 5% of the tumor area were noted. Immunohistochemical staining revealed that the tumor cells were diffusely placental alkaline phosphatase and vimentin positive, and focally cytokeratin positive. These findings are consistent with a tubular seminoma. The differential diagnoses are discussed.
MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation
Authors: Fujii Takeshi , Kawai Toshiro , Saito Ken , Hishima Tsunekazu , Hayashi Yukiko , Imura Joji , Hironaka Mitsugu , Hosoya Yoshinori , Koike Morio , Fukayama Masashi
Published: March 2003

Foregut‐derived neuroendocrine (NE) tumors occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN1) syndrome. Thirty‐nine sporadic NE tumors of foregut derivation (six thymic, 21 bronchial, three gastric, and nine pancreatic tumors) as well as two hindgut‐derived rectal carcinoids for somatic MEN1 gene mutation were analyzed by direct sequencing analysis. Five tumors showed mutations: nonsense mutations (Q393X and R98X) in thymic and pancreatic NE tumors, respectively, a 4 b.p. deletion (357del4) in a gastric NE carcinoma, and missense mutations (D172Y and S178Y) in pancreatic NE tumors. No mutation was identified in pulmonary or rectal NE tumors. In a patient with a pancreatic NE tumor (D172Y), the corresponding germline DNA showed the same mutation, suggesting that sporadic MEN1 syndrome was masked in this case. Somatic MEN1 gene mutations and deletions may play a crucial role in the tumorigenesis of a subset of foregut‐derived NE tumors. Sporadic MEN1 syndrome may occur as a sporadic NE tumor of the pancreas.
Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice
Authors: Nakatsuru Syuichi , Terada Miho , Nishihara Miyuki , Kamogawa Junji , Miyazaki Tatsuhiko , Qu Wei‐Min , Morimoto Koji , Yazawa Chie , Ogasawara Hideaki , Abe Yoriko , Fukui Keiko , Ichien Go , Ito Mitsuko R. , Mori Shiro , Nakamura Yusuke , Nose Masato
Published: March 2003

An MRL strain of mice bearing a Fas‐deletion mutant gene, lpr, MRL/MpJ‐lpr/lpr (MRL/lpr) develops collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjögren’s syndrome, respectively. Development of such lesions seems dependent on host genetic background since the congenic C3H/HeJ‐lpr/lpr (C3H/lpr) mice rarely develop them. To identify the gene loci affecting each lesion, a genetic dissection of these complex pathological manifestations was carried out. First, histopathological features in MRL/lpr, C3H/lpr, (MRL/lpr × C3H/lpr) F1 intercross, and MRL/lpr × (MRL/lpr × C3H/lpr) F1 backcross mice were analyzed. Genomic DNA of the backcross mice were subjected to association studies by Chi‐squared analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. As a result, gene loci recessively associated with each lesion were mapped on different chromosomal positions. We concluded that each of these lesions in MRL/lpr mice is under the control of a different set of genes, suggesting that the complex pathological manifestations of collagen disease result from polygenic inheritance.
Pathologic, cytologic and immunohistochemical findings of an intra‐abdominal desmoplastic small round cell tumor in a 15‐year‐old male
Authors: Takekawa Yoshinori , Ugajin Wakato , Koide Hiroshi , Nishio Satoshi , Yamamoto Tomoko , Sawada Tatsuo
Published: March 2003

The intra‐abdominal desmoplastic small round cell tumor is a rare neoplasm. It usually occurs in young males and diffusely involves the peritoneum and pursues an aggressive clinical course. The present patient was a 15‐year‐old male who experienced abdominal pain and abdominal swelling. The patient was diagnosed with an intestinal myogenic sarcoma, and surgery for tumor resection was performed in June 1999. The tumor was a 20 × 15 × 15 cm well‐defined mass in the peritoneum involving the transverse colon and stomach with peritoneal disseminations and splenic metastasis. Microscopic findings were well‐defined nests composed of small round cells and separated by abundant desmoplastic stroma. Cytologically, the tumor cells consisted of small, round to oval cells with a scant amount of light blue cytoplasm. Immunohistochemically, the tumor cells were positive for anti‐epithelial membrane antigen, vimentin, desmin, neuron‐specific enolase and WT1 protein antibodies. Similar pathologic features with other small round cell tumors may lead to differential diagnostic difficulties that require the application of ancillary diagnostic methods, such as immunohistochemistry and cytogenetic techniques.
Ileal carcinoid tumor complicating carcinoid heart disease and secondary retroperitoneal fibrosis
Authors: Sakai Daisuke , Murakami Masato , Kawazoe Kazuya , Tsutsumi Yutaka
Published: March 2003

A 70‐year‐old man with metastatic liver tumors showed carcinoid syndrome with clinical symptoms of facial flushing, palpitation, dyspnea, and an itching sensation. Regurgitation of the tricuspid and aortic valves was observed by echocardiography. An elevated serum level of serotonin and a high urine excretion of serotonin metabolites were confirmed. Autopsy confirmed a serotonin‐immunoreactive 1 cm ileal carcinoid tumor with metastasis to the liver, bone and peritoneum. The tumor cells were argyrophilic but not argentaffin, and showed erythrophagocytosis in the primary lesion. All the four heart valves and bilateral atrial endocardium showed fibromyxoid thickening, indicating the association of carcinoid heart disease. Desmoplastic reaction with deposition of sulfated acid mucopolysaccharides was also observed in the retroperitoneal space (secondary retroperitoneal fibrosis). Stenosis of the bilateral ureters and inferior mesenteric artery provoked hydronephrosis and lethal ischemic necrosis of the left‐sided colon, respectively. Rarity of functioning ileal carcinoid tumor and pathogenesis of systemic fibroplasia are discussed.
p73: Structure and function
Authors: Ichimiya Shingo , Nakagawara Akira , Sakuma Yuji , Kimura Sachiko , Ikeda Tatsuru , Satoh Masaaki , Takahashi Nobuaki , Sato Noriyuki , Mori Michio
Published: March 2003

Alteration of the p53 tumor suppressor gene is a common, if not general, observation in human malignant tumors. p73 Is a novel member of the p53 family at chromosome 1p36.3, at which locus frequent defects are seen in many tumors including neuroblastoma. Besides structural similarities, the fact that p73 functions in the regulation of the cell cycle and apoptosis promotes the expansion of the research field concerning p53‐associated tumor progression. In this paper, we review the structure and function of p73 as well as the mutational status in various human tumors. In addition, possibilities for new therapeutic applications with p73 for cancer cell control are discussed.
Analysis of the immunoglobulin heavy chain gene of secondary diffuse large B‐cell lymphoma that subsequently developed in four cases with B‐cell chronic lymphocytic leukemia or lymphoplasmacytoid lymphoma (Richter syndrome)
Authors: Nakamura Naoya , Kuze Tetsuo , Hashimoto Yuko , Hoshi Sayuri , Tominaga Kunihiko , Sasaki Yoshikazu , Shirakawa Asumi , Sato Michiko , Maeda Kunihiko , Abe Masafumi
Published: March 2003

The immunoglobulin heavy chain gene (IgH gene) was analysed in four cases of B‐cell Richter syndrome, in order to determine whether a secondary diffuse large B‐cell lymphoma (DLBCL) could arise from the same clone as the initial B‐cell chronic lymphocytic leukemia (B‐CLL) and lymphoplasmacytoid lymphoma (LPL) or be a de novo event, and whether secondary DLBCL shows an intraclonal microheterogeneity. Both the initial B‐CLL and secondary DLBCL in two cases expressed CD5 antigen. Both samples of the initial B‐CLL or LPL and the secondary DLBCL in three cases were examined for comparison. The polymerase chain reaction‐amplified IgH gene of secondary DLBCL in two cases (CD5+ case and CD5− case) were different from those of the initial B‐CLL, revealing a new malignant clone. The other case (CD5−) showed that secondary DLBCL had a sequence identical to the initial LPL, indicating the same clonal origin. The variable region of the IgH gene of secondary DLBCL (CD5+ two cases and CD5− two cases) exhibited a 0.5–9.0% somatic mutation range and no intraclonal microheterogeneity.
Hepatoid variant of yolk sac tumor of the testis
Authors: Horie Yasushi , Kato Masako
Published: March 2003

A case of testicular yolk sac tumor (endodermal sinus tumor) consisting predominantly of hepatoid cells is documented. A mass measuring approximately 4 × 3 cm was noted in the left testis of a 64‐year‐old man. Preoperative examination revealed an elevated serum level of α‐fetoprotein (5479 ng/mL). Histologically, the lesion was composed predominantly of sheet‐like or trabecular proliferation of hepatocyte‐like cells with eosinophilic or clear cytoplasm. The tumor cells were immunoreactive for α‐fetoprotein, antimitochondrial antibody, cytokeratin (AE1/AE3), α‐1‐antichymotrypsin, α‐1‐antitrypsin, albumin, carcinoembryonic antigen and epithelial membrane antigen. It was necessary to distinguish this variant lesion from metastatic hepatocellular carcinoma, embryonal carcinoma and hepatoid carcinoma.
Elastosis in lung carcinoma: Immunohistochemical, ultrastructural and clinical studies
Authors: Fukushima Mitsuhiro , Fukuda Yuh , Kawamoto Masashi , Yamanaka Nobuaki
Published: March 2003

Elastosis is the pathological finding of focal deposits of elastic fibers in abnormal amounts within tissue. It is well described in the case of infiltrating carcinoma of the breast, but elastosis in lung carcinoma has not been previously documented in detail. We investigated the characteristics of elastosis in lung carcinoma with light and electron microscopies, and immunohistochemistry for α‐1‐antitrypsin. A total of 184 surgically resected primary lung carcinomas were studied. Elastosis was detected in adenocarcinomas (85/106), squamous cell carcinomas (11/60) and adenosquamous carcinomas (5/7), but not in small‐cell carcinomas (n = 4) or large‐cell carcinomas (n = 5). The degree of elastosis in each case was divided into one of five grades, graded as 3+ to 1–. The score of elastosis was significantly higher in adenocarcinoma than that in squamous‐cell carcinoma (P < 0.01). In the cases of adenocarcinoma, the mean score of elastosis in the well‐differentiated type (WD n = 43) was higher than that in the moderately differentiated (MD) (n = 39; P = 0.012) and poorly differentiated (PD) types (n = 24; P < 0.01). The mean score of elastosis in MD adenocarcinoma was also higher than that in the PD type (P < 0.01). Light‐ and electron‐microscopic analyses revealed that these elastic fibers in elastosis were composed of aggregates of thick mature and fine immature elastic fibers, and were positive for α‐1‐antitrypsin. It is suggested that both degraded elastic fibers and newly synthesized fibers are contained in the elastosis of lung carcinoma. Although no significant evidence was detected to suggest any correlation between elastosis and the degree of tumor invasion, the survival curves of adenocarcinomas with elastosis showed a significantly improved prognosis than of those without elastosis in the cases of stages IA and IB (n = 52; P = 0.026).
Immunohistochemical inactivation of p14ARF concomitant with MDM2 overexpression inversely correlates with p53 overexpression in oral squamous cell carcinoma
Authors: Sano Takaaki , Hikino Toshiaki , Xue Qi , Saito Tadashi , Kashiwabara Kenji , Oyama Tetsunari , Nakajima Takashi
Published: March 2003

The CDKN2 gene encodes two structurally different proteins: a cyclin‐dependent kinase inhibitor called p16, which regulates retinoblastoma protein (pRb)‐dependent G1 arrest, and a cell cycle inhibitor designated p14ARF, which arrests cell growth in G1‐S and also in G2‐M. Whereas inactivation of p16 has been described as a frequent event in various cancers, including oral cancer, the current function of p14ARF is still poorly understood. A physical association between p14ARF and MDM2 blocks MDM2‐induced p53 degradation, resulting in increased levels of p53, which in turn leads to cell cycle arrest. The present study immunohistochemically examined the expression of p16 and p14ARF together with pRb, MDM2 and p53 status in a series of oral cancers. The results showed that p14ARF was frequently absent in the oral cancers (15/37, 41%) as was p16 immunostaining. Concomitant immunopositivity for p14ARF and MDM2 overexpression was frequently observed in a subset of the cancers, whereas an inverse correlation between p14ARF and MDM2 expression and the diffuse staining of p53 was clearly detected. Moreover, the results showed that in most cases of oral cancer (35/37, 95%) at least one protein was altered, and lymph node metastasis was more frequent in the tumors with alterations in both the p16/pRb and p14ARF/p53 pathway (8/16, 50%) than in the tumors with one or no alteration of these two major pathways.
Clinicopathological study of a hilar nodule in the livers of long‐term survivors with biliary atresia
Authors: Ijiri Rieko , Tanaka Yukichi , Kato Keisuke , Misugi Kazuaki , Ohama Yokatsu , Shinkai Masato , Nishi Toshiji , Aida Noriko , Kondo Fukuo
Published: March 2003

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill‐defined nodule‐like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long‐term survivors, compared to the patients with nodule‐like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well‐preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule‐like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well‐preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less‐affected hepatic tissues.
Tubal ectopic pregnancy associated with an adenomatoid tumor
Authors: Inoue Teruhiko , Nabeshima Kazuki , Shimao Yoshiya , Akiyama Yutaka , Ohtsuka Teruo , Koono Masashi
Published: March 2003

We present a case of coexistence of an ectopic pregnancy and an adenomatoid tumor in the same fallopian tube. The adenomatoid tumor is the most common benign neoplasm of the fallopian tube, and the vast majority of ectopic pregnancies occur in the fallopian tube. However, coexistence of these two conditions is extremely rare, and there has been only one previously reported case in the English literature. In the present case, the placental tissue, consisting of chorionic villi and decidua, was present in the ampulla, and the adenomatoid tumor was found in the myosalpinx, just proximal to the implantation site, replacing a large part of the myosalpinx. The close spatial relationship of these two lesions suggests that an adenomatoid tumor could have interfered with transportation of the fertilized ovum through the tube, possibly via impaired contractile activity of the myosalpinx, and consequently caused the ectopic tubal pregnancy.
Cell differentiation and apoptosis of monocytic and promyelocytic leukemia cells (U‐937 and HL‐60) by tryptanthrin, an active ingredient of Polygonum tinctorium Lour.
Authors: Kimoto Tetsuo , Hino Keiko , Koya‐Miyata Satomi , Yamamoto Yukiko , Takeuchi Makoto , Nishizaki Yasushi , Micallef Mark J. , Ushio Shimpei , Iwaki Kanso , Ikeda Masao , Kurimoto Masashi
Published: March 2003

Tryptanthrin, a bioactive ingredient of Polygonum tinctorium Lour., is a member of the Indigo plant family and has potent cytocidal effects on various human leukemia cells in vitro. At low concentrations, tryptanthrin enhanced the expression of cell differentiation (CD) markers in human monocytic (U‐937) and promyelocytic (HL‐60) leukemia cells indicative of differentiation to monocytes/macrophages. Furthermore, nitroblue tetrazolium (NBT) reductive and α‐naphthyl butyrate esterase (NBE) activities were markedly increased after treatment. Tryptanthrin was more potent than dimethyl sulfoxide (DMSO) at inducing U‐937 cell differentiation into monocytes/macrophages. After treatment with higher concentrations of tryptanthrin for 24 h, cytoplasmic vacuolation and destruction of mitochondria were observed. The leukemia cells died via apoptosis 48 h after treatment. Cytoplasmic vacuolation and apoptotic changes correlated with the dysfunction of mitochondria. Electron microscopic observations revealed marked swelling and destruction of mitochondria after exposure of the leukemia cells to tryptanthrin. Exposure to tryptanthrin enhanced Fas‐induced apoptosis and increased caspase‐3 activity before induction of apoptosis. These results show that low concentrations of tryptanthrin can induce differentiation of leukemia cells but higher concentrations will kill leukemia cells through apoptosis, possibly through a caspase‐3/Fas antigen pathway.
Adenocarcinoma arising in gastric heterotopic pancreas: Clinicopathological and immunohistochemical study with genetic analysis of a case
Authors: Osanai Makoto , Miyokawa Naoyuki , Tamaki Tohru , Yonekawa Motoki , Kawamura Akio , Sawada Norimasa
Published: March 2003

Heterotopic pancreas in the stomach is a relatively common congenital condition, but the risk of malignant transformation is extremely low. In this study, we describe a case of adenocarcinoma arising from a gastric heterotopic pancreas and we consider its morphological and immunohistochemical features and genetic analysis, in order to examine its histogenesis. This unusual sequela was seen in a 57‐year‐old woman. Image studies showed a protruding lesion with a central ulcer located in the lesser curvature from the angle to the body of the stomach. A biopsy specimen confirmed this lesion as adenocarcinoma before total gastrectomy. The tumor showed mixed patterns of solid neoplastic‐cell proliferation and moderately differentiated glandular structures, and also showed transitional lesions to obvious malignancy, that is, dysplasia, or adenocarcinoma in situ. Neoplastic cells had positive immunoreactivity for carbohydrate antigen (CA) 19‐9, mucin (MUC) 1, and insulin, and the mutant allele‐specific amplification method revealed a point mutation at K‐ras codon 12 (GGT [Gly]→GAT [Asp]), which is the most common mutational change observed in patients with pancreatic carcinoma. The features of the present case provide clear evidence that this tumor originated from heterotopic pancreatic tissue rather than from gastric epithelium.
Cytokeratin subtypes in biliary atresia: Immunohistochemical study
Authors: Sasaki Hideyuki , Nio Masaki , Iwami Daiji , Funaki Nobuo , Ohi Ryoji , Sasano Hironobu
Published: March 2003

The etiology of biliary atresia (BA) remains unknown, but ductal‐plate malformation and insufficient ductal‐plate remodeling have been suggested to play important roles, so it is beneficial to examine the maturation and differentiation of bile ducts in BA. Different epithelial types are characterized by the expression of specific cytokeratin (CK) subtypes. CK can therefore serve as a ‘lineage marker’ of epithelial cells. CK subtypes have not been previously examined in BA. In this study, we examined the maturation of bile‐duct cells in BA (n = 45) using immunohistochemistry of CK subtypes, with mouse monoclonal antibodies to CAM5.2, and CK subtypes 7, 8, 13, 14, 17, 19 and 20. We then compared these findings with pediatric non‐BA (n = 11) and fetal (n = 21) liver. We semiquantitatively evaluated the findings using a H score method. In the fetal liver, immunoreactivity for CAM5.2, CK‐7, CK‐8 and CK‐19 was detected in bile‐duct cells, and CAM5.2 and CK‐8 immunoreactivity was also detected in hepatocytes. The distribution of these CK subtypes was the same in fetal, pediatric non‐BA and BA liver. However, CK‐7 immunoreactivity was markedly weaker in bile ducts of fetal (H scores: ductal plate 0 ± 0; remodeling 9.5 ± 40.3; remodeled 37.3 ± 60.8) and BA (H score: 200.9 ± 55.3) liver compared to non‐BA liver (H score: 251.1 ± 33.5). In addition, CK‐20 was detected in the bile ducts of the fetal and BA liver, but not in non‐BA liver. These findings suggest that the expression patterns of CK subtypes in bile‐duct cells in BA are similar to that in developing bile‐duct cells, which is indicative of bile‐duct cell immaturity.
Non‐neoplastic glandular structures in a benign peripheral nerve sheath tumor
Authors: Kusumi Tomomi , Tanaka Masanori , Kurita Takeaki , Murata Azuma , Kato Masashi , Kato Satoru , Kudo Hajime
Published: March 2003

It is a recognized fact that glandular structures sometimes occur in peripheral nerve sheath tumors (PNST). Reports indicate that epithelial potential could be expressed in malignant PNST, while the glands in most benign PNST could be trapped skin adnexa. We present a case of spindle cell tumor with glandular structures. The patient was a 55‐year‐old man who had a subcutaneous tumor excised. The spindle cell tumor had histological characteristics of neurofibroma. The glandular structures had a pattern of immunohistochemical staining that was similar to that of the secretory coils and excretory ducts of normal eccrine glands. Therefore, the glands were thought to be naturally existing eccrine glands. The glands were completely enclosed within the tumor and not connected to one another; a cluster formation was not observed. The upper portion of tumor included some glands of skin adnexa. The spindle cell tumor may have originated from the nerves distributed around the skin adnexa, and grown to the subcutaneous tissue. The glands may have been left behind rather than have been trapped in the tumor.
Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in two patients with von Hippel–Lindau disease
Authors: Hamazaki Shuji , Nakashima Hiroyuki , Matsumoto Kengo , Taguchi Kohji , Okada Shigeru
Published: March 2003

Here we report tumor‐to‐tumor metastases identified in two patients with von Hippel–Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor‐to‐tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis.
The World Health Organization classification of malignant lymphoma: Incidence and clinical prognosis in HTLV‐1‐endemic area of Fukuoka
Authors: Ohshima Koichi , Suzumiya Junji , Kikuchi Masahiro
Published: March 2003

New insights into the pathogenesis of lymphoid malignancies have been gained through novel genetic, molecular and immunological techniques. A new classification system for lymphoid malignancies, known as the new World Health Organization (WHO) classification, has been proposed recently based on these findings. The relative incidence of the subtypes of malignant lymphoma is known to differ according to geographic location. Adult T‐cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T‐cell leukemia virus type 1 (HTLV‐1), and the Kyushu islands are an HTLV‐1 endemic area. To clarify the relationship between the histological classification and prognosis of lymphoid malignancies, we reclassified previous cases in our department and summarized our previous reports using the WHO classification. Of 933 cases of lymphoid malignancies, 471 (50%) were B‐cell lymphoma, 396 (42%) T/natural killer (NK)‐cell lymphoma and 41 (4%) Hodgkin lymphoma (HL). Analysis of clinical outcome showed favorable prognosis for HL, intermediate for B‐cell lymphoma and poor prognosis for T‐cell lymphoma. Among B‐cell lymphomas, the commonest type was diffuse large B‐cell lymphoma (n = 281; 60%). Marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT) was diagnosed in 82 cases (17%), follicular lymphoma in 52 (11%) and mantle cell lymphoma in 24 (5%). Other less common lymphomas were Burkitt lymphoma (n= 9; 2%) and lymphoblastic lymphoma (n = 5; 1%). Using overall survival rates, the various B‐cell lymphoma types could be divided into three broad groups for prognostic purposes: (i) low‐risk group comprising follicular lymphoma and MALT; (ii) intermediate‐risk group comprising diffuse large B‐cell lymphoma and Burkitt lymphoma; and (iii) high‐risk group comprising mantle cell lymphoma and lymphoblastic lymphoma. Among the T/NK‐cell lymphomas, the commonest type was ATLL (n = 191; 48%), followed by peripheral T‐cell lymphoma, unspecified (n = 83; 21%), angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) (n = 38; 10%), anaplastic large cell lymphoma (ALCL) (n = 22; 6%). Less common types were lymphoblastic lymphoma (n = 17; 4%), nasal and nasal‐type NK/T‐cell lymphoma (n = 17; 4%), mycosis fungoides (MF) (n = 9; 2%) and other rare types. With respect to clinical prognosis, T/NK‐cell lymphomas fell into three groups: (i) relative low‐risk group comprising ALCL, AILD, MF and lymphoblastic lymphoma; (ii) relative intermediate‐risk group comprising NK/T‐cell lymphoma and unspecified lymphoma; and (iii) extremely high‐risk group comprising ATLL. Among the lymphoblastic lymphomas, B‐cell type and T‐cell type lymphomas exhibited different clinical outcomes. We conclude that the histological, phenotypic and genotypic classification of the new WHO system should be beneficial for the clinical approach to these tumors.
Overexpression of p16 and p14ARF is associated with human papillomavirus infection in cervical squamous cell carcinoma and dysplasia
Authors: Sano Takaaki , Masuda Norihiro , Oyama Tetsunari , Nakajima Takashi
Published: March 2003

The CDKN2 gene encodes two structurally different proteins: a cyclin‐dependent kinase inhibitor, p16, which regulates retinoblastoma protein (pRb)‐dependent G1 arrest, and a cell cycle inhibitor, p14ARF, which blocks MDM2‐induced p53 degradation resulting in an increase in p53 levels that leads to cell cycle arrest. Recent studies have revealed that expression of p16 and p14ARF is influenced markedly by the status of pRb and p53, and p16 overexpression has been demonstrated in cervical neoplasia because of functional inactivation of pRb by the human papillomavirus (HPV) E7 protein. To clarify the p14ARF status and the relationship between p16/p14ARF and other cell cycle molecules in cervical carcinogenesis, immunohistochemical analysis of p16, p14ARF, p53 and MDM2 was performed on 65 samples of cervical and genital condylomatous and neoplastic lesions, including nine HPV‐negative tumors. In most cervical cancers and preneoplastic lesions with HPV infection of high and intermediate risk, a marked overexpression of p14ARF as well as the p16 protein (i.e. dotted nuclear immunostaining) was observed. All condyloma acuminata except one and low‐grade dysplasia with HPV infection of low risk, such as HPV 6, immunohistochemically showed completely negative staining for p14ARF, also seen in non‐neoplastic and mesenchymal cells. Our results clearly show that the mode of p14ARF overexpression in cervical neoplastic cells with HPV association differs from that in cancers of other organs without HPV association, and the p14ARF overexpression may be attributable to a negative feedback result in the functional inactivation of the pRb and p53 proteins by HPV oncoproteins.
Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathy
Authors: Liu Diange , Razzaque Mohammed S. , Nazneen Arifa , Naito Takashi , Taguchi Takashi
Published: March 2003

The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen‐binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47‐expressing cells were identified as α‐smooth muscle actin‐positive myofibroblasts and vimentin‐positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy.
Upregulation of α‐synuclein by lipopolysaccharide and interleukin‐1 in human macrophages
Authors: Tanji Kunikazu , Mori Fumiaki , Imaizumi Tadaatsu , Yoshida Hidemi , Matsumiya Tomoh , Tamo Wakako , Yoshimoto Makoto , Odagiri Hiroki , Sasaki Mutsuo , Takahashi Hitoshi , Satoh Kei , Wakabayashi Koichi
Published: March 2003

α‐Synuclein was originally identified as the presynaptic nerve terminal protein. Recently, we reported that α‐synuclein is also expressed in cultured human astrocytes and that its levels are increased by stimulation with interleukin‐1β, suggesting that it may be involved in inflammatory processes. We therefore investigated the effect of inflammatory stimuli on α‐synuclein expression in human macrophages. α‐Synuclein mRNA and protein were detected in cultured human macrophages and levels of α‐synuclein protein were increased by stimulation with lipopolysaccharide and interleukin‐1β in a time‐ and concentration‐dependent manner. Immunofluorescent staining showed that α‐synuclein protein was expressed within the cytoplasm and nucleus. Furthermore, α‐synuclein immunoreactivity was present in alveolar macrophages from human lung tissues. These findings suggest that the function of α‐synuclein is not exclusive to the nervous system and that α‐synuclein may play a role in inflammatory processes and immune responses.
Pleomorphic hyalinizing angiectatic tumor of soft parts: A case report and literature review
Authors: Matsumoto Koshi , Yamamoto Taiich
Published: March 2003

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, recently recognized neoplasm occurring predominantly in the subcutaneous tissue of the lower limbs of adults. We report a case of PHAT in an 83‐year‐old woman who presented with a 5.0 × 5.0 × 2.0 cm mass in the soft part of her left thigh. Histologically, the tumor was well circumscribed by a thin fibrous capsule and predominantly composed of fusiform cells with eosinophilic cytoplasm and round‐to‐oval or pleomorphic nuclei. The tumor cells resembled those of malignant fibrous histiocytoma, but differed from them by less prominent mitotic figures. Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34; partially positive for vimentin and CD99 (MIC‐2); and negative for epithelial and non‐epithelial markers. Ultrastructurally, the tumor cells had pleomorphic cytoplasm and nucleus. Intermediate‐sized cytoplasmic filaments were observed in a few tumor cells, but neurosecretory‐type granule‐like intracytoplasmic organelles were not seen. These findings suggest that this tumor is derived from stromal fibroblast, such as solitary fibrous tumors or giant cell angiofibroma.
Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits: Characterization of capillary sprouting by ultrastructural 3‐D reconstruction study
Authors: Ebina Toshihito , Hoshi Naoto , Kobayashi Mikio , Kawamura Koichi , Nanjo Hiroshi , Sugita Akihiro , Sugiyama Tatsuo , Masuda Hirotake , Xu Chengpei
Published: March 2003

Physiological angiogenesis occurs in electrically stimulated skeletal muscles. It is known to start as capillary sproutings, but has not yet been well characterized as ordinary angiogenesis. To characterize the sprouting process during physiological angiogenesis, we carried out an ultrastructural 3‐D reconstruction study for the extensor digitorum longus of three adult rabbits under electrical stimulation for 7 days. In addition, hemodynamic and morphological studies were carried out after stimulation for 3, 7, and 14 days. The electrical stimulation induced a twofold increase in femoral artery blood flow and tissue blood flow. This was associated with an increase in capillary density of the muscle by more than twofold at 7 and 14 days. Sproutings frequently appeared at 7 days (4.3 ± 1.4 × 103 sproutings per mm3, 13.3 ± 6.9 µm in length). All sprouting tips consisted of endothelial cytoplasmic protrusions (ECP). Besides sproutings, there were communicating networks consisting segmentally of ECP (11.6 ± 5.6 × 103 networks per mm3). Endothelial cytoplasmic protrusions began to appear at 3 days, were frequent at 7 days, and disappeared at 14 days, which corresponded well to the changes in blood flow and capillary density. We consider that in physiological angiogenesis, sproutings start as ECP, which contact other capillaries to form networks and become hollowed to form new capillary networks.
Malignant phyllodes tumor of the prostate: Retrospective review of specimens obtained by sequential transurethral resection
Authors: Watanabe Masatoshi , Yamada Yasushi , Kato Hiroya , Imai Hiroshi , Nakano Hiroshi , Araki Tomio , Shiraishi Taizo
Published: March 2003

A case of malignant phyllodes tumor of the prostate in a 67‐year‐old man is reported. The patient was referred to a hospital for urinary retention. From material taken at three transurethral resections of the prostate (TURP), a histological diagnosis of benign prostatic hyperplasia was made. However, at the fourth TURP, phyllodes tumor was diagnosed due to the presence of elongated epithelial ducts and proliferating cellular stroma with mitosis and nuclear atypia. Two months later, total cystoprostatectomy was performed. Histologically, the tumor was composed of dysplastic stromal cells and irregularly elongated epithelial ducts. Five months later the patient developed multiple lung and pelvic lymph node metastases and died. This report documents progression to a higher histological grade of prostatic phyllodes tumor documented with sequential pathological findings obtained from four TURP and surgical specimens over about 3 years.
Pulmonary fibrosis: Cellular and molecular events
Authors: Razzaque Mohammed S. , Taguchi Takashi
Published: March 2003

Connective tissue remodeling of the interstitium is an important feature of chronic lung diseases encompassing interstitial inflammatory changes and subsequent pulmonary fibrosis. The early inflammatory phase is usually associated with the release of several cytokines and chemokines by activated resident cells and infiltrating cells which, in turn, help further recruit inflammatory mononuclear cells. Cytokines and growth factors secreted by inflammatory cells and by interstitial cells (fibroblasts and myofibroblasts) play an important role in the fibrogenic phase of pulmonary fibrosis by inducing matrix synthesis. In addition, matrix‐degrading enzymes and their inhibitors also contribute to extracellular matrix (ECM) remodeling in pulmonary fibrosis. This review addresses the pathophysiology of wound healing and different phases of pulmonary fibrosis.
Modified Campbell diagram to assess respiratory muscle action in speech
Authors: Johnston Sharn , Yan Sheng , Sliwinski Pawel , Macklem Peter T
Published: March 2003

Ten normal and four moderate to severe stutterers participated in the study. Pleural (Ppl) and abdominal (Pab) pressure was studied using oesophageal and gastric balloon catheter systems and VL (VL) was studied using magnetometry. The classical Campbell diagram was modified by plotting Pab versus VL. In a preliminary study we determined whether a surrogate curve could be substituted for the true curve in the Campbell diagram. We obtained true relaxation curves in six subjects. We obtained surrogate chest wall relaxation curves by joining the Pab value at functional residual capacity (FRC) to a point on the dynamic expiratory Pab,VL curve where Pab had decreased to half its maximum inspiratory excursion. In order to obtain the mirror image of the elastic recoil curve of the lung subjects breathed slowly from FRC to total lung capacity. Dynamic Pab,VL and Ppl,VL measurements during quiet breathing and speech were superimposed on static lung and chest wall curves. The simultaneous plot of Ppl and Pab provided a continuous measure of transdiaphragmatic pressure as a function of VL. We inferred non‐diaphragmatic muscle recruitment vis‐à‐vis the diaphragm by the relationship of Pab to Ppl and Pab to the relaxation curve. We compared dynamic Ppl during phonation with that during breath‐holding with the glottis open at the same VL, as an estimate of subglottic pressure (Psg). Analysis of variance testing showed that the true, surrogate and predicted relaxation slopes were not significantly different. The strategies that stutterers used to speak were either higher or lower VL than normal subjects and they had a different pattern of respiratory muscle recruitment. Stutterers were unable to achieve the appropriate degree of recruitment to develop and maintain a normal Psg for conversational speech and this contributed to dysfluency. We conclude that the quiet breathing loops can provide a reasonable approximation to the relaxation curve in normal healthy subjects and that modifications to the Campbell diagram provide useful means of measuring Psg and assessing respiratory muscle recruitment patterns.
Macleod’s syndrome presenting with spontaneous pneumothorax
Authors: Soni Rajeev , Branes David
Published: March 2003

A 19‐year‐old woman with a recent history of recurrent bronchitis presented with a spontaneous left pneumothorax. Review of the chest radiographs revealed features of Macleod’s syndrome on the same side, with unilateral lucency and hypoplastic hilar vessels. To our knowledge this is the first report of Macleod’s syndrome presenting with spontaneous pneumothorax.
Multi‐organ failure caused by reactivated coccidioidomycosis without dissemination in a patient with renal transplantation
Authors: Cha Jae Myung , Jung Saera , Bahng Hye Seung , Lim Chae Man , Han Duck Jong , Woo Jun Hee , Koh Younsuck
Published: March 2003

Objective:

The acute respiratory failure caused by pulmonary coccidioidomycosis without dissemination is an extremely unusual event.

Case Report: We report a 47‐year‐old renal transplanted man with a reactivated pulmonary coccidioidomycosis, whose clinical course presented as fulminant respiratory failure, disseminated intravascular coagulation and profound hypotension mimicking bacterial pneumonia and septic shock. Lung biopsy showed conglomerated necrotizing granulomas containing many spherules filled with endospores of Coccidioides immitis.

Conclusion: Coccidioidomycosis should be included in the differential diagnosis of acute sepsis, particularly in an immunocompromised host who has travelled in an endemic area.