bluuebunny/crossref_metadata_2025 huggingface dataset:
Proliferative activity and tumor angiogenesis is closely correlated to stromal cellularity of fibroadenoma: Proposal fibroadenoma, cellular variant
Authors: Hasebe Takahiro , Imoto Sigeru , Sasaki Satoshi , Tsubono Yoshitaka , Mukai Kiyoshi
Published: March 2003

Fibroadenoma (FA) is the most common benign tumor of the breast in adult women. Some FA have a highly cellular stroma, making it difficult to differentiate from phyllodes tumors (PT). Forty‐three FA were grouped into: (i) 27 conventional type (FACT) median stromal cellularity (SC) of highest cellular area (HCA), 125 cells/1 high‐power field (HPF); and (ii) 16 cellular variant (FACV) median SC of HCA, 125 cells/1 HPF. These were studied for the proliferative activity of their stromal cells. Expression of c‐fos, p53, basic fibroblast growth factor (bFGF), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor (VEGF) in the stromal cells were examined in the FA and 12 PT to determine whether it is possible to separate FACV from FACT. The proliferative activity of stromal cells was evaluated by the labeling index (LI) of proliferating cell nuclear antigen (PCNA). Conventional type fibroadenoma stromal cells had the lowest frequency of c‐fos, p53, bFGF, FGFR and VEGF protein expression; PT stromal cells had the highest frequency of expression; and FACV stromal cells had an intermediate frequency of expression. Multivariate analysis demonstrated that bFGF and FGFR expression are significantly correlated with SC of FA. Separation of FACV from FACT by SC seems appropriate in revealing the phenotypic and biological differences of FA. The SC of FA seems to be regulated by bFGF and FGFR expression.
Langerhans cell histiocytosis of the stomach with atypical morphological features
Authors: Terracciano Luigi , Kocher Thomas , Cathomas Gieri , Bubendorf Lukas , Lehmann Frank Serge
Published: March 2003

We report the unique case of a 52‐year‐old patient with atypical morphological features of gastric Langerhans cell histiocytosis. The man was admitted because of increasing upper abdominal pain and weight loss. The upper gastrointestinal endoscopy showed a submucous, hemispherical tumor of the stomach wall along the lesser curvature. The tumor was completely removed and the patient was discharged 11 days later. Two months later, he died at home. The cause of death is unknown, because the autopsy was denied by the relatives. Macroscopically, the stomach showed a 4.5 × 2.5 cm large, spherical tumor of the lesser curvature of the corpus, which infiltrated the perigastric omenta and lymph nodes, the distal pancreas and the glissonian liver capsule. The vast majority of neoplastic cells were intensely positive for S‐100 and CD1a. Typical Birbeck granules could be identified in almost all cells. Cell nuclei analyzed by flow cytometry showed an aneuploid peak, a feature typically associated with malignant disease.
Assessment of DNA content in formalin‐fixed, paraffin‐embedded tissue of lung cancer by laser scanning cytometer
Authors: Kamiya Noriki , Yokose Tomoyuki , Kiyomatsu Yoshimasa , Fahey Michael T , Kodama Tetsuro , Mukai Kiyoshi
Published: March 2003

A new cytometric device, a laser scanning cytometer was developed to overcome the limitations of flow cytometry (FCM) and image analyses. The purpose of this study was to develop a method that allows laser scanning cytometry (LSC) to be used for measuring the cellular DNA content of paraffin‐embedded tissues. Paraffin‐embedded lung cancer tissue from 30 patients was analyzed by both FCM (p‐FCM) and LSC (p‐LSC). In addition, touch preparations from fresh frozen tissues were prepared to provide material for LSC (f‐LSC). The limits of agreement for the DNA indices (DI) measured by p‐LSC and p‐FCM were –0.07 to 0.07, indicating that for a given case, these methods would be expected to differ by no more than 0.07. The limits of agreement for comparisons between the other materials and methods were wider and depended upon the size of the measurements. Agreement between f‐LSC and p‐FCM was good for small DI values, but poor for large values. Agreement between f‐LSC and p‐LSC was poor for small and large DI values, but good for moderately sized values. Discordancies in DNA ploidy status between different materials and methods may have been caused by either the heterogeneity within tumors, sampling errors or differences in the interpretation of histograms. This method allows a comparison of the results of DNA analysis with histologic findings from hematoxylineosin‐stained sections and the prognosis of the patients.
Immunohistochemical study of MIB1 expression in phyllodes tumor and fibroadenoma
Authors: Umekita Yoshihisa , Yoshida Hiroki
Published: March 2003

The histogenesis of phyllodes tumor (PT) and fibroadenoma (FA) is closely related, and discrimination between them by histopathological analysis is sometimes problematic. Moreover, objective criteria by which to categorize the grade of malignancy in PT are still controversial. The aim in this study is to clarify whether immunohistochemical evaluation using the MIB1 antibody, which reacts with the ki‐67 antigen, correlates with the histological grade of malignancy in PT, and can discriminate between PT and FA. The 47 cases of phyllodes tumor (PT) were categorized into three groups (malignant, 4 cases; borderline, 6 cases; benign, 37 cases) according to the criteria proposed by Azzopardi (1979) and were investigated by immunohistochemistry. There were significant differences in stromal MIB1‐index among the three groups (P< 0.0001), and, unexpectedly, benign PT was easily divided into two groups according only to the MIB1‐index. There were significant differences in the stromal MIB1‐index (P< 0.001) and stromal cellularity (P< 0.01) between the two benign PT groups. A total of 478 cases of FA was reviewed and these were divided into 403 conventional fibroadenomas (CFA), 36 cellular fibroadenomas (CEFA) and 39 fibroadenomas with focal phyllodes structure (FAPS). All cases of CEFA and FAPS, and 140 cases of CFA were studied by immunohistochemistry. The 21/215 (9.8%) cases of FA, which were designated as FAMIB, showed a high stromal MlB1‐index (more than 10/0.0625 mm
2). Conversely, 77% cases of FA showed no MIB1‐positive stromal cells. The incidence of MIB1‐positive epithelium of FAMIB was much higher than that of FA. These results suggest that high proliferative activity may be present in both stromal and epithelial cells of FAMIB. Our study suggests that immunohistochemical evaluation using MIB1 antibody correlates with the histological grade of malignancy in PT, and can select FA with high proliferative activity. However, new objective diagnostic factors useful for discriminating FA from benign PT with a low MIB1‐index should be developed.
Expression of scavenger receptor class A and CD14 in lipopolysaccharide‐induced lung injury
Authors: Yamamoto Takashi , Ebe Yusuke , Hasegawa Go , Kataoka Masashi , Yamamoto Shunsuke , Naito Makoto
Published: March 2003

CD14 and macrophage scavenger receptor class A type I and II (MSR‐A) are receptors for lipopolysaccharide (LPS). In this study, the expressions of both receptors in the lung after administration of LPS in aerosol to mice with a nebulizer were observed. Bronchiolar epithelial cells and alveolar macrophages immediately incorporated LPS and expressed CD14. CD14‐positive neutrophils then appeared in the alveolar space followed by the appearance of MSR‐A‐expressing cells in the vascular lumen, pulmonary interstitium, and alveolar space. Numbers of apoptotic cells increased after 1 day, and MSR‐A‐expressing macrophages actively incorporated apoptotic bodies. Daily administration of macrophage colony stimulating factor (M‐CSF) to the mice resulted in increased levels of MSR‐A expression and reduced levels of CD14 as well as several cytokine expressions, leading to shortening of the inflammatory process. The numbers of apoptotic cells were reduced in M‐CSF injected mice. These findings imply that CD14 acts as an immediate expressing receptor for LPS and MSR‐A exerts a protective function by scavenging LPS and apoptotic cells in LPS‐induced lung injury.
Pineal malignant rhabdoid tumor with chondroid formation in an adult
Authors: Sugita Yasuo , Takahashi Yoshihiko , Hayashi Itsurou , Morimatsu Minoru , Okamoto Kenichi , Shigemori Minoru
Published: March 2003

A pineal tumour in a 27‐year‐old male is presented with the characteristic histological features of a pineal malignant rhabdoid tumor (MRT) with chondroid formation. Occasionally, tumor cells contained a single well‐demarcated hyaline globular inclusion within the cytoplasm adjacent to the nucleus. The stroma of these tumors tends to be densely hyalinized and become chondroid. Immunohistochemical staining was positive for vimentin, epithelial membrane antigen, chromogranin A, synaptophysin, neuron‐specific enolase, S‐100 protein, and muscle actin. Despite surgery and radiochemotherapy, the tumor recurred in the pineal region and metastasized to the lower lobe of right lung. The patient died 2 years after the initial diagnosis. This is the second published case of central nervous system‐MRT appearing in an adult. The clinical and pathological features of pineal MRT in this patient are presented.
Immunohistochemical detection of cytokeratin and epithelial membrane antigen in leiomyosarcoma: A systematic study of 100 cases
Authors: Iwata Jun , Fletcher Christopher D. M.
Published: March 2003

Although ‘aberrant’ expression of the epithelial markers, cytokeratin (CK) and epithelial membrane antigen (EMA), in leiomyosarcoma has been described previously, there has not been a study of this phenomenon with clinicopathological correlation in a large series of lesions at different anatomical sites. We investigated systematically the immunohistochemical reactivity for CK and EMA in 100 cases of leiomyosarcoma. CK and EMA were positive in 38% and 44% of the cases, respectively. Although staining was usually focal, extensive immunoreactivity was observed in 11% with CK and 6% with EMA. There was no correlation between immunoreactivity for CK and EMA in leiomyosarcomas and non‐neoplastic smooth muscle at the same location. Immunoreactivity for CK and EMA was not correlated with the location, age, sex, histological grade, or histological features, except for more frequent EMA positivity in vascular and uterine tumors than in soft tissue cases. These results indicate that CK and/or EMA‐positive leiomyosarcomas do not have distinctive clinicopathological features differing from those of negative cases. However, the considerable frequency of immunoreactivity for these epithelial markers in leiomyosarcoma, occasionally with diffuse and strong immunopositivity, should be recognized as a potentially serious diagnostic pitfall in the differential diagnosis of other malignant spindle cell neoplasms.
Application of short tandem repeat of genomic DNA and mitochondrial DNA for identification of mixed‐up tissue specimens
Authors: Sano Kenji , Takayanagi Kayoko , Kaneko Taimei , Liu Chunyan , Kinoshita Tomoyuki , Nakamura Naoshi , Asamura Hideki , Ito Makoto , Fukushima Hirofumi , Hotchi Masao
Published: March 2003

Deoxyribonucleic acid (DNA) typing methods, short tandem repeat of genomic DNA and mitochondrial DNA with the use of polymerase chain reaction amplification, were applied to formalin‐fixed, paraffin‐embedded tissues submitted for diagnosis, to identify and sort out mixed‐up tissue specimens. These techniques were found to be reliable, reproducible and specific for personal identification, and thus to eliminate the need for further examinations and to prevent unnecessary surgery.
Extrauterine Müllerian adenosarcoma of the peritoneum with an extensive rhabdomyosarcomatous element and a marked myxoid change
Authors: Kato Noriko , Zhe Jin , Endoh Yasushi , Motoyama Teiichi
Published: March 2003

A case of extrauterine Müllerian adenosarcoma of the peritoneum in a 20‐year‐old woman is reported. The tumor was widely based on the abdominopelvic wall and there were no unusual features in the genital organs. The cut surface of the tumor showed a marked gelatinous appearance. The tumor was composed of an admixture of benign Müllerian‐type epithelium and sarcomatous stroma. The predominant element of the sarcomatous area was rhabdomyosarcoma, which showed a close resemblance to well‐differentiated embryonal rhabdomyosarcoma. In another sarcomatous area, fibroblastic cells without myoblastic properties diffusely proliferated in a marked myxoid background with some collagen bundles. Both the mitotic count and Ki‐67 proliferative index of these cells were lower than those of rhabdomyoblastic cells. On follow up, the patient was disease free for 1 year postoperatively, without any subsequent treatment. The present case indicates that extrauterine adenosarcoma can also show histological heterogeneity as do uterine adenosarcomas. The remarkable myxoid change of this tumor seemed to be more largely due to a fibromyxoid element than a rhabdomyosarcomatous element, and the coexistence of the former may be related to the less aggressive behavior of this tumor.
A human B‐lineage dendritic cell line, HBM‐Noda and its potential role in human T‐cell leukemia/lymphoma virus type I infection
Authors: Nagasaki Makoto , Morikawa Shigeru , Torii Ikuko , Zhang Jie , Morikawa Keiko
Published: March 2003

An Epstein–Barr virus‐transformed B‐cell line, HBM‐Noda (Noda), that has a dendritic morphology as well as several characteristic features of dendritic cells (DC) has been established. We therefore refer to Noda as B‐lineage DC. Although human T‐cell leukemia/lymphoma virus type I (HTLV‐I) exhibit substantial cellular tropism, the roles of DC in HTLV‐I infection remain unknown. To further clarify the characteristics of Noda cells, we performed infection experiments using a concentrated HTLV‐I fraction from the adult T‐cell leukemia cell line, HPB‐ATL‐2. Noda, as well as other cell lines examined, were sensitive to HTLV‐I infection as detected by proviral DNA using polymerase chain reaction, but most infected Noda cells underwent necrosis within 7 days. The most striking feature of Noda cells was the abundant expression of viral antigen (p19) on the cell surface following infection (approximately day 4), probably due to strong viral adsorption. In cocultivation experiments using Noda cells at day 1 of post‐infection and peripheral blood activated T cells, we detected a few (1.3%) viral antigen expressing T cells after 5 days of coculture by flow cytometry. These results suggest that B‐lineage DC such as Noda cells play a role in the establishment of HTLV‐I infection at an early phase.
Apoptosis, anoikis and their relevance to the pathobiology of colon cancer
Authors: Shanmugathasan Minalini , Jothy Serge
Published: March 2003

The maintenance of a constant number of cells in an adult organism is a tightly regulated process. This is particularly important in organs where cells are in a constant rate of renewal during the entire lifespan. In these organs, cell number homeostasis is the direct consequence of a bal‐ance between cell proliferation and apoptosis. The colonic epithelium is an example of such a site and the high prevalence of colon cancer makes the understanding of cell number homeostasis more important to define. Normal colonic epithelium is organized in crypts where cell proliferation, migration, differentiation and apoptosis are topographically organized in a linear fashion along the crypt axis. Normal colonic crypts are composed of stem cells at the base, a proliferation and a differentiation zone in the lower third of the crypt, a migration zone in the upper two‐thirds, and the surface epithelium where senescent cells are eliminated by apoptosis. Globally, apoptosis can be defined as a normal process of cell suicide, critical for development and tissue homeostasis. Colonic epithelial cells migrate from the base of the crypt to the surface epithelium in 6–7 days. The normal architecture of the crypt is maintained by a balance between cell proliferation at the base and apoptosis at the top of the crypt and surface epithelium.
Comparative immunohistochemical analysis of developing kidneys, nephroblastomas and related tumors: Considerations on their histogenesis
Authors: Satoh Fumiko , Tsutsumi Yutaka , Yokoyama Seishichi , Osamura R. Yoshiyuki
Published: March 2003

Immunoperoxidase analysis was performed to evaluate the phenotypic expression of eight renal differentiation antigens in five nephroblastomas, one clear cell sarcoma of the kidney (CCSK), one rhabdoid tumor of the kidney (RTK), and four related tumors. A total of 19 fetal and pediatric kidneys, including two 6th‐week mesonephric tissues, were comparatively studied. All the specimens were fixed in formalin and embedded in paraffin. Neural cell adhesion molecule (NCAM), a marker of the nephrogenic zone of the developing kidney, was consistently expressed in the epithelial and blastematous components of nephroblastomas of the common type. The epithelial components also commonly expressed NK1 and Leu 7 (CD57), and the findings may reflect that both were positive in immature proximal tubules directly differentiating from the NCAM‐positive immature fetal tubuloglomerular buds. In two cases, the epithelial component was immunoreactive for CD10 and WT1 gene product (WT1‐GP). Leu M1, epithelial membrane antigen and CA15–3 were only focally expressed in nephroblastomas. Rhabdomyoblasts in the stroma were positive for WT1‐GP. CCSK was featured by the expression of NCAM and CD10. In RTK, focal epithelial differentiation was discerned, with focal positivity of WT1‐GP and negativity of NCAM. In congenital mesoblastic nephroma, the stromal spindle cells were strongly immunoreactive for WT1‐GP, while WT1‐GP was not expressed in solitary multilocular cyst of the kidney. Pancortical nephroblastomatosis was featured by the diffuse subcapsular reappearance of immature metanephric tissue. Nephroblastomas and related conditions thus offer an adequate model for studying human nephrogenesis.
An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema and pleural effusion
Authors: Semba Shuho , Moriya Takuya , Youssef Emile M , Sasano Hironobu
Published: March 2003

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of ovulation induction with exogenous gonadotropins, such as human menopausal gonadotropin and follicle‐stimulating hormone. These hormones are considered to increase capillary permeability and cause third space fluid shift. We report an autopsy case of severe OHSS in a 28‐year‐old Japanese female. The patient developed bilateral chest pain and progressive dyspnea during the course of administration of human gonadotropins. Pleural effusion and hypouresis clinically disappeared 4 days after the onset of the symptoms, but the patient died suddenly of rapid respiratory insufficiency. Autopsy examination revealed massive pulmonary edema, intra‐alveolar hemorrhage and pleural effusion without any evidence of pulmonary thromboembolism. Histopathological examination of the ovary demonstrated multiple well‐developed follicle formations, consistent with OHSS. It is very important to recognize that massive pulmonary edema can occur in a patient with OHSS. To the best of our knowledge, this is the first autopsy report of a patient with severe OHSS.
Immunohistochemical expression of neural tissue markers (neuron‐specific enolase, glial fibrillary acidic protein, S100 protein) in ameloblastic fibrodentinoma: A comparative study with ameloblastic fibroma
Authors: Takeda Yasunori , Sato Hirotaka , Satoh Masanobu , Nakamura Shin‐ichi , Yamamoto Hirotsugu
Published: March 2003

Formalin‐fixed paraffin‐embedded sections of three cases of ameloblastic fibrodentinoma (AFD) were studied by the avidin–biotin–peroxidase complex method using antibodies against neuron‐specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S100 protein and the results were compared with those in ameloblastic fibroma (AF). A striking histopathological characteristic of AFD was the formation of abortive dentin with various degrees of maturation at the epithelial–mesenchymal tissue interface. Central cells of enamel organ‐like epithelia with various stages of abortive dentin induction in AFD were generally positive for NSE. Dental lamina‐like epithelial cells also showed positive staining in some areas. No cells were positive for NSE in AF. Positive staining for GFAP was observed in the juxta‐epithelial mesenchymal tissue of the formation stage of immature dentin with various numbers of entrapped cells in AFD, but GFAP staining was negative in other mesenchymal and epithelial tissues at other stages. In AF, no GFAP‐positive cells were found. There were a few S100 protein‐positive cells found in the foci of epithelial components in both AFD and AF. Mesenchymal cells showing a dendritic or spindle shape were positive for S100 protein in some areas of AFD and AF. Although such cells in the mesenchymal component of pigmented AFD were more numerous than in non‐pigmented AFD and AF, their distribution pattern in the former condition was basically similar to that in the latter. Although the present results, obtained from conventional immunohistochemical procedures, do not directly reflect the expression of neural crest‐derived cells in the dentinogenesis of AFD, such results do not disprove the possibility of the expression of neural proteins probably related to neural crest‐derived cells in dentinogenesis under certain pathologic conditions in odontogenic mixed tumors. Such a phenomenon may also occur during dentinogenesis in other odontogenic mixed tumors and in normal tooth differentiation, but at an undetectable level.
The World Health Organization classification of malignant lymphomas in Japan: Incidence of recently recognized entities
Authors: Pathologists *Lymphoma Study Group of Japanese
Published: March 2003

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non‐Hodgkin's lymphoma (2189 cases (68.53%) of B‐cell lymphoma, 796 cases (24.92%) of T‐cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non‐Hodgkin's lymphoma were 33.34% for diffuse large B‐cell lymphoma, 8.45% for marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T‐cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T‐cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal‐type T/NK cell lymphoma, 2.35% for angioimmunoblastic T‐cell lymphoma, and 2.35% for precursor B‐cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T‐cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large‐cell lymphoma of T‐ and null‐cell types (1.53%), and B‐cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south‐western Japanese island, Kyushu, an endemic area of human T‐cell leukemia virus type 1 (HTLV‐1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV‐1.
Intrathyroidal branchial cleft‐like cyst in chronic thyroiditis
Authors: Haba Reiji , Miki Hiroshi , Kobayashi Shoji , Kushida Yoshio , Saoo Kousuke , Hirakawa Eiichiro , Ohmori Masaki
Published: March 2003

An extremely rare case of intrathyroidal branchial cleft‐like cyst is reported. A 71‐year‐old man complained of a growing mass in the right lateral neck. A cystic mass in the upper lobe of the right thyroid was demonstrated by ultrasonography and computed tomography. The surgical specimen revealed a cystic mass with dense fibrous capsule, 22 × 20 × 10 mm in size. Microscopically, the cyst walls and the surrounding thyroid tissue contained severe lymphoid cell infiltration with lymphoid follicle. Squamous epithelium lined the cyst wall. Immunohistochemically, squamous epithelium was positive for keratin, cytokeratin 19, carcinoembryonic antigen, and epithelial membrane antigen, but negative for calcitonin and chromogranin A. The patient is currently well with no evidence or recurrence for 43 months.
Phosphoglyceride crystal deposition disease
Authors: Miura Katsutoshi , Fukuda Hiroshi , Mineta Hiroyuki , Yamaguchi Kazue , Harada Hidekazu , Yusa Hiroshi , Tsutsui Yoshihiro
Published: March 2003

An extremely rare phosphoglyceride deposition disease is reported. A healthy 62‐year‐old Japanese woman suffered from tumors that repeatedly appeared in injured soft tissues for more than 20 years. No immunologic disorders or abnormal laboratory data were found. Histology showed foreign body granulomas consisting of macrophages surrounding yellowish‐white crystals. The crystals were weakly positive by von Kossa's method, were dissolved in 30% acetic acid with gas, and were easily dissolved in 0.1 N NaOH or potassium hydroxide, losing their crystal structure. Using a scanning electron microscopy X‐ray microanalyzer, phosphorus and calcium peaks were detected. Phosphoglycerides were detected by microscopic infrared spectrophotometry and microsampling mass spectrometry. The gold hydroxamic acid method for detecting phosphoglyceride showed strong positive staining in the crystals. Based on the above analyses, the deposited crystals were regarded as phosphoglyceride, which bound calcium as a counter ion. The crystals tended to be deposited at sites of injury, where macrophages had accumulated. The patient had received many injections of a medicine made from alcohol extract from bovine liver. We suspect that this medicine was related to the cause of the deposition as the deposition repeatedly appeared at the site of the injections.
Inhibitory effects of antisense oligonucleotides on the expression of procollagen type III gene in mouse hepatic stellate cells transformed by simian virus 40
Authors: Horie Satoshi , Kitamura Yukisato , Kawasaki Hironaka , Terada Tadashi
Published: March 2003

The effects of phosphorothioate antisense oligonucleotides (ASO), complementary to the AUG start region, the junctional region of the intron and exon, and to exon of the procollagen type III gene, were investigated in a mouse hepatic stellate cell (HSC) line transformed by the simian virus 40 gene, SV68c‐IS cells. ASO were transfected by lipofection. Immunohistochemistry, western and northern blotting showed inhibitory effects on procollagen type III gene expression by ASO that were complementary to the AUG start region and the junctional region of the intron and exon 2. However, ASO complementary to the exon 2 and 3, junctional region of the intron and exon 3, and sense oligonucleotides complementary to each ASO did not show any inhibitory effects. The effects of ASO complementary to the AUG start region were greater than those of ASO complementary to the junctional region. The effects of ASO were transient and a large amount of ASO was required to induce inhibitory effects without lipofection. ASO were effective in inhibiting the expression of the procollagen type III gene in the HSC which is well known to play a critical role in liver fibrosis.
Primary giant cell tumor of soft tissues similar to bone giant cell tumor: A case report and literature review
Authors: Rodríguez‐Peralto José L. , Lopez‐Barea Fernando , Fernandez‐Delgado Jorge
Published: March 2003

In this report we describe a primary giant cell tumor (GCT) of soft tissues located in the left dorsal wrist of a 52‐year‐old man. Plain radiographs did not reveal any lesion in his carpal or hand bones. Although the tumor was clinically considered a ganglion initially, the microscopic features were identical to those found in classic GCT of bone. Light microscopy showed a lesion composed of a homogeneously mixed proliferation of spindle and polygonal mononucleated stromal cells and evenly distributed multinucleated, osteoclast‐like giant cells. Whereas most bone tumors have an extraosseous counterpart, only 13 cases of GCT in soft tissues had been published until 1998. Moreover, 64 new cases have been reported in three series. Nevertheless, most major reviews and textbooks do not consider this tumor as a specific entity and regard it as a low grade variant of malignant GCT of soft tissue. We describe the clinical, histologic, and immunohistochemical features of this rare benign neoplasm emphasizing the differential diagnosis with its malignant soft tissue counterpart, an ominous tumor.
Expression of CD31, Met/hepatocyte growth factor receptor and bone morphogenetic protein in bone metastasis of osteosarcoma
Authors: Arihiro Koji , Inai Kouki
Published: March 2003

The mechanism of metastasis of osteosarcoma cells to other bones has not yet fully been clarified. The purpose of the present study was to examine whether various factors involve the formation of osteosarcoma metastatic foci in other bones. Immunohistochemically, CD31 expression in osteosarcoma with no bone metastasis and osteosarcoma with bone metastasis was noted in 10 and 75% of cases, respectively. Met/hepatocyte growth factor (HGF) receptor expression in osteosarcoma with no bone metastasis and osteosarcoma with bone metastasis was noted in 90 and 25% of cases, respectively. Bone morphogenetic protein (BMP) expression in osteosarcoma with no bone metastasis and osteosarcoma with bone metastasis was noted in 20 and 75% of cases, respectively. Metastasis of osteosar‐coma cells to other bones was significantly correlated with expression of BMP and CD31 and with no expression of Met/HGF receptor protein in osteosarcoma cells. In contrast, expression of insulin‐like growth factor receptor in osteosarcoma cells did not correlate significantly with bone metastasis. These results suggest that formation of metastatic foci of osteosarcoma cells in other bones is regulated by CD31, which is associated with migration between endothelial cells, by BMP, which can induce and activate various mesenchymal cells affecting bone formation, and by escape of effect by HGF, which promotes differentiation of osteosarcoma cells.
Hepatocellular carcinoma arising in non‐alcoholic steatohepatitis
Authors: Zen Yoh , Katayanagi Kazuyoshi , Tsuneyama Koichi , Harada Kenichi , Araki Ichirou , Nakanuma Yasuni
Published: March 2003

The incidence and significance of hepatocellular carcinoma (HCC) in non‐alcoholic steatohepatitis (NASH) has not been previously evaluated in detail. We recently experienced a case of NASH with multicentric HCC in a female patient. At the age of 58 years, the patient was diagnosed with non‐insulin‐dependent diabetes mellitus, treated by insulin therapy. The patient did not drink alcohol. She was negative for all serological markers of hepatitis B and C virus infection. Because of liver dysfunction, a needle biopsy was performed at the age of 62 years, and pathological findings, such as fatty change, Mallory's body, nuclear glycogen and pericellular fibrosis, suggested a diagnosis of NASH. Subsequently, four nodules were detected in the liver by imaging. Liver biopsies were performed from each nodule. One nodule was pathologically diagnosed as a pseudolymphoma, while three other nodules were moderately differentiated HCC (10 years after the diagnosis of non‐alcoholic steatohepatitis), well‐differentiated HCC (11 years later) and dysplastic nodule (11 years later), suggesting multicentric occurrence of HCC. This case suggests that HCC could be a late complication of NASH.
Multicentric telangiectatic osteosarcoma
Authors: Park Yong‐Koo , Joo Mee
Published: March 2003

A rare case of multicentric telangiectatic osteosarcoma in a 29‐year‐old woman is described. A plain X‐ray showed a pure osteolytic lesion of the navicular, cuboid and I, II, III cuneiform bones. On magnetic resonance images, a T1‐weighted image showed heterogeneous low signal intensity. A T2‐weighted image showed heterogeneous high signal change with multicentric cystic foci and fluid–fluid levels. Histologically, the lesion showed typical telangiectatic osteosarcoma with numerous atypical giant cells.
Glomerular expression of α‐smooth muscle actin reflects disease activity of IgA nephropathy
Authors: Kaneko Yoko , Nakazawa Koh , Higuchi Makoto , Hora Kazuhiko , Shigematsu Hidekazu
Published: March 2003

To elucidate the relationship between histological disease states and clinicopathological features in immunoglobulin A nephropathy (IgAN), 90 needle‐biopsy specimens diagnosed as IgAN were analyzed. The specimens were divided into four groups according to histological grade and stage index. Immunohistochemical features of α‐smooth muscle actin (α‐SMA), macrophages positive for myeloid/histiocyte antigen (MAC387), and expression of type I, III and IV collagens were all examined. Glomerular expression scores of α‐SMA and the degree of intraglomerular macrophage infiltration were highest in the active and non‐sclerotic groups. Type I and IV collagens were significantly more abundant in the sclerotic groups than in the active groups. Type III collagen was strongly expressed in both the active and sclerotic groups. Double immunolabeling of α‐SMA and intercellular adhesion molecule (ICAM)‐1 revealed that ICAM‐1 was expressed around the α‐SMA‐positive mesangial area. In multivariate analysis, the glomerular expression score of α‐SMA was mostly correlated with histological grading in the 10 clinicopathological parameters. Type IV collagen score was mostly correlated with histological staging. These results suggest that glomerular α‐SMA expression reflects the histological activity of IgAN. Immunohistological staining of α‐SMA is valuable to estimate the degree of disease activity in IgAN.
Modified and simplified western blotting protocol: Use of intermittent microwave irradiation (IMWI) and 5% skim milk to improve binding specificity
Authors: Li Wei , Murai Yoshihiro , Okada Eikichi , Matsui Kazuhiro , Hayashi Shinichi , Horie Masaki , Takano Yasuo
Published: March 2003

A modified western blotting protocol was developed to increase the binding specificity of antigens and antibodies, using intermittent microwave irradiation (IMWI) with seven antibodies and two cell lines. The method was based on IMWI of the blotting membrane in the immunoblotting step using 5% skim milk as the diluting buffer. For some antibodies against p53, CDK4 and cyclinE, there were no distinct differences between the IMWI(+) and IMWI(–) counterparts; but improvement over the standard protocol was noted in both. For some antibodies, such as the polyclonal antibody against tubulin and the monoclonal antibodies against β‐tubulin, cyclinA and cyclinB1 (which were otherwise difficult to obtain good results with), IMWI was extremely effective, resulting in clear, specifically binding bands and a clean background. Moreover, the times were reduced from 8 to 3 h. Both the IMWI(+) and IMWI(–) protocols can be applied as simple, rapid and highly specific detection techniques for applications with various antigens, reducing background ‘noise’ to a minimum.
Pigmented neuroendocrine tumor of the lung, showing neuromelanin
Authors: Iihara Kuniko , Yamaguchi Kazuyoshi , Fujioka Yasunori , Uno Sumiko
Published: March 2003

A pigmented neuroendocrine tumor was discovered incidentally in a 62‐year‐old woman through examination by chest computed tomography. The tumor was located in the left lower lobe, S6, of the lung and was 8 mm in diameter. The preoperative percutaneous needle biopsy was interpreted as a tumor suggestive of small cell carcinoma. Histological examination of the operated lobectomy material revealed that the nodule was a neuroendocrine tumor consisting of mainly spindle‐shaped cells and several pigmented cells. Electron microscopy showed several dense‐core neurosecretory‐type granules in tumor cells, as well as abundant, pleomorphic electron‐dense granules in pigmented cells much larger in size and most consistent with lipofuscin or neuromelanin. No melanosomes or premelanosomes were identified. Considering the result of ultrastructural and histochemical studies, the pigment was considered most likely neuromelanin. Neuromelanin is found in neurons of substantia nigra and locus ceruleus, and sympathetic ganglion cells. It is rarely found in neuroendocrine tumors and we review the available reports regarding pigmented carcinoid tumor.
Osteopontin is involved in the formation of epithelioid granuloma and bile duct injury in primary biliary cirrhosis
Authors: Harada Kenichi , Ozaki Satoru , Sudo Yoshiko , Tsuneyama Koichi , Ohta Hajime , Nakanuma Yasuni
Published: March 2003

Recently, it was shown that osteopontin (OPN) is involved as a chemoattractant cytokine in the recruitment of macrophages and T lymphocytes in the granulomas of diverse etiologies and also plays an important role in the production of autoantibodies and development of autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by immune‐mediated bile duct damage with frequent epithelioid granulomas. In this study, the expression of OPN was immunohistochemically examined in 25 PBC and 52 control livers. Epithelioid cells within granuloma in PBC expressed OPN variably. These cells were also positive for CD68, suggesting their histiocyte/macrophage lineage. In addition, strong expression of OPN was seen in the cytoplasm of mononuclear cells infiltrating around granulomas and also damaged bile ducts in PBC. The number of such positive mononuclear cells and the ratio of OPN‐positive cells/total infiltrating cells in portal tracts were higher in PBC than in controls. The majority of these OPN‐positive cells were found to be IgG‐ or IgM‐producing plasma cells. These suggest that in PBC, OPN is an important immune molecule in portal tracts, and contributes to the recruitment of mononuclear cells into epithelioid granuloma and also participates in bile duct injury via B‐cell differentiation and plasma cell expansion.
Biogeography of sexual and asexual populations inBostrychia moritziana(Rhodomelaceae, Rhodophyta)
Authors: West John A. , Zuccarello Giuseppe C.
Published: March 2003

Bostrychia moritziana(Sonder ex Kützing) J. Agardh is recorded from many regions around the world. Our laboratory culture investigations have verified a sexual life cycle in isolates from Australia, Venezuela, Colombia, South Africa, Fiji, New Zealand and Indonesia. By contrast, asexual isolates producing successive generations of tetrasporophytes in laboratory culture and, presumably, in the field, are known from Australia. New Caledonia and Japan. In Australia, asexual reproduction is absent only in Victoria. In Western Australia, Northern Territory and Queensland, 99% of the isolates have asexual reproduction. In New South Wales (NSW), asexual and sexual populations are often intermixed. Of the 176 worldwide field collections, 58% were vegetative, 39% were tetrasporic, 2% were female and 1% were male. After several years of observations on the asexual isolates in culture, at least 30 successive asexual tetrasporophytic generations have developed. Only two asexual isolates (3558 and 3575) from NSW have formed a single male and female gametophyte in culture. In a self‐cross of 3568, the carpospores developed into tetrasporophytes that recycled asexually. All outcrosses done with normal sexual isolates produced normal carposporophytes and the carpospores developed into tetrasporophytes that also recycled asexually. Asexual populations may arise repeatedly by loss of meiosis in tetrasporangia of sexual populations. Asexual reproduction apparently does not diminish the overall dispersal and abundance in the field. Our present bio‐geographic data show that sexually reproducing popuiations ofB. moritzianaoccur worldwide, while asexuaily reproducing populations are confined to the western Pacific.Bostrychia bisporaWest et Zuccarello, initially described on the basis of its asexual reproduction to distinguish it fromB, moritziana, is now reduced to synonymy withB. moritziana.
Rapid extraction of high‐quality genomic DNA from Porphyra yezoensis (Bangiales, Rhodophyta)
Authors: Nakajima Maiko , Kitade Yukihiro , Iitsuka Osamu , Fukuda Satoru , Saga Naotsune
Published: March 2003

We developed a simple, rapid and stable method for extraction of high molecular weight DNA from the marine red alga Porphyra yezoensis Ueda using both guanidium treatment and QIAGEN™ kit (Funakoshi, Tokyo, Japan). The method does not require expensive equipment and complex steps. The DNA yield averaged 1.5 μg 100 mg−1 of Porphyra tissue and the A260/A280 and A230/A260 ratios of the DNA were approximately 1.8 and 0.4, respectively. It was of sufficient quality to be used for not only polymerase chain reactions but also other DNA manipulation techniques such as restriction digestion and construction of genomic libraries.
An exotic pulmonary infection in Thailand: Melioidosis
Authors: Maneechotesuwan Kittipong
Published: March 2003

Melioidosis is an infectious disease from Burkholderia pseudomallei and is confined in specific geographic areas such as Southeast Asia. Its highest prevalence in Thailand is in the north‐eastern part. Most infected patients had worked paddy fields or had underlying diseases such as diabetes mellitus. Melioidosis can manifest clinically, with either disseminated or localized features. In the disseminated form patients developed an acute and progressive course with septicaemia. In contrast, patients with the localized form usually presented with prolonged fever, and symptoms of one or more organ involvement, in particular the lung and the liver. Definite diagnosis of melioidosis is made by an isolation of Burkholderia pseudomallei from a variety of clinical specimens. Treatment of choice for the septicaemic patients is an initial combination of ceftrazidime and trimethoprime‐sulfamethoxazole, followed by trimethoprime‐sulfamethoxazole for up to 6–12 months depending on the result of clinical specimen culture. Treatment for the localized form requires simultaneous antibiotic therapy and surgical drainage. However, optimum duration of antibiotic therapy remains unknown so further research is required. Melioidosis is an important disease in terms of mortality rate and it requires rapid diagnosis and treatment. To prevent recurrence, it is necessary to continue oral doxycycline or trimethoprime‐sulfamethoxazole for 6–12 months.
Acoustic parameters of voluntary cough in healthy non‐smoking subjects
Authors: Olia Paolo Michele , Sestini Piersante , Vagliasindi Mario
Published: March 2003

Objective:

The aim of this study was to explore cough in healthy subjects.

Methodology:

We studied 234 coughs generated by 24 (12 males) healthy non‐smokers (forced expiratory volume in 1 s (FEV1) 103 ± 8% of predicted), who had no significant differences in FEV1 and age between males and females. For each subject, several bouts of voluntary coughing were recorded using a personal computer with an A/D converter (sampling rate 10 kHz, 8 bit resolution) and the first and second coughs of each bout were analysed using short‐time Fast Fourier Transformation. For each cough we studied the three phases that are produced. In particular, we studied the duration of the three parts, loudest frequency in the first part, lowest and highest frequencies, number of continuous frequencies and lowest and highest continuous frequencies in the second part, and the loudest frequency of the third part if present.

Results:

We found significant differences between males and females in length of the first part (41.4 ± 14 vs 44.7 ± 10.4 msec, P = 0.04), loudest frequency of the first part (362 ± 145 vs 449 ± 145 Hz), lowest frequencies (282 ± 100 vs 348 ± 135 Hz) and highest continuous frequencies (3877 ± 571 vs 4147 ± 362 Hz; P < 0.001) of the second part. An interesting finding was that healthy males and females had the same number of continuous frequencies. Different frequencies are probably a consequence of anatomical differences in airway geometry involved in the cough.

Conclusion:

In cough frequency spectrum studies the differences between the two sexes should be taken into account to reduce the variability of the results.
Changes in malondialdehyde levels in bronchoalveolar fluid and serum by the treatment of asthma with inhaled steroid and beta2‐agonist
Authors: Ozaras Resat , Tahan Veysel , Turkmen Serdar , Talay Fahrettin , Besirli Kazim , Aydin Seval , Uzun Hafize , Cetinkaya Ali
Published: March 2003

Objective:

Oxidative stress plays an important role in the pathogenesis of asthma. Recent data suggest that clinical indices of the patients with asthma may not correlate with the underlying inflammatory process. We aimed to measure the level of malondialdehyde (MDA), which is a marker of lipid peroxidation, a free radical‐mediated process, before and after a well‐accepted treatment of asthma.

Methodology:

Nine non‐smoking females and five non‐smoking males with mild–moderate asthma were included. Twenty‐four age‐ and sex‐matched, non‐smoking healthy people (17 females and seven males, mean age 32.1 years, range 20–59) were included for control. After initial evaluation, spirometry, broncoscopy with bronchoalveolar lavage (BAL), and blood sample were maintained. The patients were treated with twice‐daily salmeterol inhaler (100 μg/d) and fluticasone propionate inhaler (500 μg/d). One month later the investigations were repeated. Serum MDA levels before treatment were compared with both the levels after treatment and levels of controls. Malondialdehyde levels of BAL were compared before and after treatment.

Results:

Serum MDA level of the patient before treatment was 6.7 ± 0.8 nmol/mL, significantly higher than that of healthy controls; 3.8 ± 0.4, P < 0.001. One month after the treatment, serum MDA level decreased to 5.3 ± 0.7 nmol/mL (P < 0.001). However, this level is still significantly higher than healthy controls (P < 0.0001). Forced expiratory volume in 1 s level of the patients increased from 2.43 ± 0.79 L to 3.50 ± 1.21 L after the treatment (P < 0.001).

Conclusion:

Although treatment with beta2‐agonist and corticosteroid inhalers for the duration of 1 month reduced lipid peroxidation significantly, it was still at a level significantly higher than healthy controls. The treatment may need a longer duration to improve lipid peroxidation or an alternative regimen which is more effective in controlling inflammation may be warranted.
Hypoxic ventilatory depression in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes
Authors: Osanai Shinobu , Takahashi Toru , Enomoto Hiroyuki , Satoh Nobuyuki , Yahara Osamu , Akiba Yuji , Fujiuchi Satoru , Nakano Hitoshi , Ohsaki Yoshinobu , Kikuchi Kenjiro
Published: March 2003

We describe a case of a 21‐year‐old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.