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We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21-27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13-21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.

Porocarcinoma is a rare skin appendage carcinoma that may arise de novo or be associated with pre-existing poroma and hidroacanthoma simplex (HAS). Here, we report a case of porocarcinoma arising in pigmented HAS, which led to death from multiple lymph node, liver and bone metastases. A 72-year-old Japanese man presented with a brown to focal black flat plaque, measuring 17 × 12 mm, on the posterior region of his right thigh. Histopathological study of the tumor revealed that there was intraepidermal proliferation of small-sized basaloid cells, and it exhibited the ‘Jadassohn phenomenon’, with dendritic melanocytes, and a few ductal structures were observed. Continuing to the intraepidermal nests, the invasive proliferation of large polygonal cells with occasional intracytoplasmic ductal structures was observed. Carcinoembryonic antigen and epithelial membrane antigen were expressed in some carcinoma cells and they highlighted the intracytoplasmic ductal structures. Multiple lymph node, liver and bone metastases were observed, and the patient died 8 months after the initial surgery. Clinical diagnosis of HAS is extremely rare. Porocarcinoma may be associated with pre-existing HAS and sometimes shows aggressive behavior. Therefore, pigmented HAS must be included in the differential diagnosis of brown or black lesions. Ishida M, Hotta M, Kushima R, Okabe H. A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node, liver and bone metastases.

Ductal adenocarcinoma of the lacrimal gland is extremely rare; to our knowledge, only seven de novo cases and one case of ductal adenocarcinoma ex pleomorphic adenoma have been reported in the literature. Here, we report a case of ductal adenocarcinoma ex pleomorphic adenoma of the lacrimal gland. A 70-year-old Japanese female received the resection of the recurrent lacrimal gland tumor (second surgery), under the clinical diagnosis of recurrent pleomorphic adenoma, fifteen years after the initial surgical resection. The resected tumor was composed of recurrent pleomorphic adenoma and adenocarcinoma. Adenocarcinoma component showed infiltrative papillo-tubular or microcystic growth of carcinoma cells, which had pleomorphic large nuclei with prominent nucleoli and rich eosinophilic cytoplasm. Large dilated ducts with central comedonecrosis were observed. Accordingly, the diagnosis of ductal adenocarcinoma ex pleomorphic adenoma was made. The tumor recurred locally eight months after the second surgery, and tumor exenteration was performed(third surgery). The histopathological features of the third surgical specimen were as same as those of the second surgical specimen. In the previously reported eight cases and the present case of lacrimal ductal adenocarcinomas, recurrence took place in 5 cases and two patients died from multiple metastases. These data suggests that lacrimal ductal adenocarcinoma appears to have a poor prognosis, similar to salivary duct carcinoma, which is one of the most aggressive salivary carcinoma. And further study is needed to clarify the clinicopathological features of the lacrimal ductal adenocarcinoma.

Tubulin is a major component of microtubules. Class III beta-tubulin (beta III) is a neuron-associated beta-tubulin isotype and expressed in the normal central and peripheral nervous systems. According to a previous study, beta III is not expressed in normal skin and squamous cell carcinoma. However, its expression has not been examined in basal cell carcinoma (BCC) of the skin. Expression of beta III was analyzed together with neural cell adhesion molecule (NCAM), chromogranin A, synaptophysin, epithelial membrane antigen (EMA) and cytokeratin (CK) 20 by immunohistochemical methods in 10 non-neoplastic skin tissues and 50 BCCs. In the normal skin, immunoreactivity to beta III was restricted to the nerve bundles in the dermis and subcutis, no positivity was shown in epithelial cells of the epidermis and skin appendages. beta III and NCAM were expressed in 50 and 68% of BCCs, respectively, predominantly periphery of tumor nests, although the distribution of both markers was not always identical. Chromogranin A, synaptophysin and CK 20 were not expressed in any of BCCs. EMA was focally expressed in only 8% of BCCs. beta III is a potential candidate for inclusion to the panel of immunohistochemical markers to distinguish small BCCs from non-neoplastic hair buds, because non-neoplastic hair follicles are not positive for beta III.

IgG4-related sclerosing disease can occur in the cardiovascular system and some inflammatory abdominal aortic aneurysms have been shown to belong to IgG4-related sclerosing disease. Herein is reported a case of IgG4-related inflammatory aortic aneurysm of the aortic arch. A 71-year-old Japanese man was found to have an aneurysm of the aortic arch with maximum dimension of 5.5 cm. The surgically resected aneurysm wall had conspicuous fibrosclerotic changes, dense lymphoplasmacytic infiltration and occasional obliterative phlebitis in the adventitia; the thickness of the adventitia was 6.5 mm. Immunohistochemistry indicated numerous IgG4-positive plasma cell infiltrates; 84% of the IgG-bearing cells were IgG4 positive. The diagnosis of IgG4-related inflammatory aortic aneurysm of the aortic arch was made. Although previously reported IgG4-related inflammatory aortic aneurysms were confined to the abdominal aorta, the present case report demonstrates that IgG4-related inflammatory aortic aneurysm can occur in the aortic arch, thereby extending the spectrum of IgG4-related periaortitis. Further studies are needed to clarify the spectrum of IgG4-related sclerosing disease in the cardiovascular system.

The value of autotransfusion is widely recognized in the surgical community and may be of increasing importance in prevention of acquired immunodeficiency syndrome and hepatitis. The concern of possible contamination of the blood with urine, bacteria in urine or viable tumor cells has limited the wide use of intraoperative autotransfusion (IAT) in urological operation. There have been no experimental reports about protection of the blood from such contamination. To investigate separation of the blood from a contaminated mixture by using an autotransfusion machine, Haemonetic Cell Saver, a study composed of three experiments was performed. First, 200 ml of blood was mixed 200 ml of urine, and thereafter, the mixture was processed by the machine and the concentration erythrocytes were collected in a bag. Biochemical analysis of the collected erythrocyte solution (CES) was performed. Second, 200 ml of blood was mixed with 200 ml of urine that was adjusted to contain each 10(7)/ml of four bacterial strains. The bacteriological study of the CES was performed. Third, 200 ml of blood was mixed with 200 ml of urine that was adjusted to contain 10(7) cancer cells. Two cell lines, KK47 originated from human bladder cancer and ACHN originated from human renal cell carcinoma was used. The cytological study of the CES was performed. The results of these experiments were: Urine constituents were completely removed from the mixture. However, all strains of bacteria could not be separated, although the number of bacteria decreased. Cancer cells were found in the CES. In conclusion IAT should be done at urological operation in selected patients that have sterile urine and do not have tumor cells in the operation field.

Primary mucinous carcinoma of the skin (MCS) is a rare skin appendage tumor and only a few cases of MCS with endocrine differentiation have been reported. Here we report an additional case of primary pure MCS with endocrine differentiation arising in the face. Histopathologically, the tumor was located in the dermis and subcutis, and nests of slight atypical epithelial cells were floating in the mucinous pools. This tumor did not accompany carcinoma in situ or invasive non-mucinous carcinoma and was difficult to differentiate from metastatic mucinous carcinoma of the skin. There was no tumor in the other organs and synaptophysin and chromogranin A were sporadically shown immunohistochemically in the tumor cells; a diagnosis of primary pure MCS with endocrine differentiation was made. MCS resembles mammary mucinous carcinoma not only in morphological appearance but also in immunohistochemical phenotypes, such as positive immunoreactivity to gross cystic disease protein fluid-15, MUC2, MUC6, estrogen receptor and progesterone receptor. It is presumed that MCS is derived from the apocrine gland, which is closely related to the mammary gland. Although endocrine differentiation is not uncommon in pure mucinous carcinoma of the breast, there have been only a few reports published on endocrine differentiation in MCS. To clarify the difference and/or similarity between mucinous carcinoma of the breast and MCS, immunohistochemical and cytogenetic analyses of additional cases of MCS are required.

Background: Recently, immunoreactivity to D2-40, a monoclonal antibody to lymphatic endothelium, was shown in a subgroup of epidermal basal cells and the majority of squamous cell carcinomas, but the immunoreactivity to this antibody has not been examined in basal cell carcinomas (BCCs) of the skin. Methods: Expression of D2-40 was analyzed together with that of cytokeratin (CK) 17, CK 19, CD34 and Ber-EP4 by immunohistochemical methods in 10 non-neoplastic skin tissue samples and 20 BCCs. Results: Immunoreactivity to D2-40 was shown in the basal cells at the outer root sheath (ORS) of hair follicles, similar to the CK 19 expression pattern. CK 17 was strongly expressed in the suprabasal cells at the ORS. D2-40 and CK 19 were focally expressed in 13/20 (65%) and 14/20 (70%) cases of BCCs, respectively, although the distributions of D2-40 and CK 19 immunoreactivity were not always identical. However, BCC cells were constantly positive for CK 17 even tumor cells that were positive for D2-40 and/or CK 19. Ber-EP4 was diffusely expressed in all BCCs, and CD34 was focally expressed in 2/20 cases. Conclusion: Our results suggested that D2-40 immunoreactivity in BCCs showed differentiation toward the ORS of hair follicles.

We have evaluated the significance of the cytopathological diagnosis of pulmonary aspergillosis using touch smears or lavage fluid obtained by the bronchoscopic examination. Thirty five cases of aspergillosis were diagnosed through the cytological examination of bronchoscopic specimens with abundant neutrophils or necrotic debris from 211 patients. Thirty three of these 35 cases were non-invasive or semi-invasive and the remaining two cases were allergic aspergillosis. Aspergilli could be cultivated from the bronchoscopic specimen only in 34% of these 35 cases. Serum beta-D glucan and galactomannan were elevated in 27% and 12% respectively. Although 92% of these 35 cases had high titer of aspergillus antibody, less than 40% of them had been suspected to be aspergillosis at the time of bronchoscopic examinations. These data clearly indicates that cytopathological examination is quite effective to make the diagnosis of pulmonary aspergillosis especially in the clinically unsuspected cases. Our experimental study revealed that Papanicolou's staining is able to color the cytoplasm of the fungal hyphae but ineffective to demonstrate empty wall of the degenerated hyphae. In our 35 aspergillosis, hyphae are frequently invisible in the slides stained with Papanicolou's method (21/35), because of the degenerative change. However, degenerated hyphae of these 21 cases were clearly demonstrated by special stain for fungi. In conclusion, application of the fungal stain to the bronchial cytological slides rich in neutrophils and/or necrotic debris is revealed to have clinical significance for the accurate diagnosis of pulmonary aspergillosis.

The expression of human epidermal growth factor receptor (HER) family proteins was examined in specimens of 52 non-small cell lung cancers to evaluate their significance in tumor cell proliferation and their response to gefitinib. Epidermal growth factor receptor (EGFR; HER1) protein was expressed most frequently (43/52 cases). HER2 and HER3 were detected in 13 and 18 cases, respectively. HER4 was detected in only one case of squamous cell carcinoma. HER3 was expressed preferentially in adenocarcinomas of the papil- lary type. In most HER3-positive cases with or without other HER family proteins, the Ki-67 labelling index (18.2%) was significantly lower than in HER3-negative cases (30.6%) (P

We have previously reported that the expression of periostin mRNA is significantly repressed in human bladder cancer tissues, and that periostin plays a role as a suppressive factor for invasion and metastasis in the progression of human bladder cancers. In this study, to clarify the role of alternative splicing of periostin in human bladder carcinogenesis, we examined the expression of wild-type (WT) and spliced variants of periostin mRNA in normal bladder and bladder cancer tissues. Although both WT and spliced periostin mRNA were expressed in all normal bladder tissues examined, no WT periostin mRNA was detected in the examined transitional cell carcinomas (TCCs) of the bladder (0/23) or in bladder cancer cell lines (0/6). Spliced variants of periostin were detected in 48% (11/23) of TCC tissues and 33% (2/6) of bladder cancer cell lines. Two types of spliced periostin (Variants I and II) were successfully isolated from bladder cancer tissues, but Variant I, which is predominantly expressed in bladder cancer tissues, did not show suppressor activity on in vitro invasiveness and in vivo metastasis of cancer cells. Immunohistochemical analysis indicated that strong belt-like expression of periostin protein was observed in the stroma just beneath the normal bladder epithelium, while it was mostly attenuated in bladder cancer tissues. These results indicate that the loss of WT periostin by down-regulation and/or alternative splicing, which produces Variant I, is closely correlated with the development of bladder cancer.

今回, われわれは扁平上皮内癌を伴った子宮頸部カルチノイド腫瘍の1症例を経験し, その細胞所見および組織所見を中心に免疫組織学的検討を加えたので報告する.症例は34歳の女性で, 細胞診で小細胞非角化型扁平上皮癌と判定され, 生検材料でも同様の診断が得られたため, 手術および治療目的で当産婦人科へ入院した.摘出標本の組織像は, 小型の異型細胞が胞巣状, 柵状, リボン状の配列を示しており, Grimelius染色では多数の好銀性顆粒がみられ, また電顕所見においても神経分泌顆粒を認めたため, カルチノイドと同定された.また扁平上皮内癌も認められたため最終的にカルチノイド腫瘍と扁平上皮内癌の重複癌と診断された.剥離細胞所見では, 円形～類円形の裸核状の異型細胞が出現しており, 核クロマチンは細～粗穎粒状を呈していた.当初これらの細胞は小細胞非角化型扁平上皮癌と判定されていたのだが, 小細胞非角化型扁平上皮癌は核クロマチンが粗顆粒状を呈することが多く, 核小体が比較的目立つという点などに注意すれば鑑別は可能であったと考える.また子宮頸部カルチノイドを診断するうえで, NSE, Leu 7が神経内分泌マーカーとして有用であった.

Estrogen receptor-related receptors (ERRs) are orphan members of the nuclear receptor superfamily. A single AGGTCA sequence element preceded by three conserved nucleotides has been identified as a specific recognition motif of ERRs. Here we performed systematic analyses of target sequences on all three ERR subtypes, alpha, beta and gamma. In electrophoretic gel-mobility shift assay and transcriptional reporter assays, they exhibited similar patterns of recognition specificities, showing extremely broad ranges of target sequences. We searched a mouse promoter database for a gene carrying possible ERR-binding sequences. The Rb-1 inducible coiled-coil 1 (Rb1cc1) gene was found to contain two putative ERR binding elements, named response element (RE)-1 and RE-2, in the promoter region. In gene reporter assays, RE-2, but not RE-1, functioned as an effective cis-regulatory element for transactivation by ERRalpha in the presence of a coactivator, peroxisome proliferator-activated receptor gamma coactivator-1alpha. Mutational analyses suggested that RE-2 is recognized by ERRalpha partly as a monovalent element, but also as a direct repeat motif separated by four spacer nucleotides. In vivo binding of ERRalpha to the Rb1cc1 promoter region was confirmed by the chromatin immunoprecipitation assay. Thus, Rb1cc1 is a target gene of ERRalpha, driven by a novel type of recognition sequence.

Peripherin is a type III neuronal intermediate filament and its expression is involved in the growth and development of the peripheral nervous systems. Peripherin expression has been reported in cutaneous endocrine carcinomas, but not in rectal well-differentiated endocrine neoplasms (carcinoid tumors). Well-differentiated endocrine neoplasms have been reported to have a relatively high incidence of metastasis, but there is no complete parameter for prediction of their malignant behavior. The aim of the present study was to clarify the expression of peripherin in human fetal and adult rectal mucosae and rectal well-differentiated endocrine neoplasms and the significance of peripherin expression in well-differentiated endocrine neoplasms. Expression of peripherin was studied immunohistochemically in 3 fetal hindgut mucosae, 10 non-neoplastic rectal mucosae, 12 rectal well-differentiated endocrine neoplasms without metastases, and 5 well-differentiated endocrine neoplasms with metastases. Adult rectal mucosal epithelial cells did not have peripherin. However, transient expression of peripherin was detected in the subgroup of epithelial cells of the fetal rectum. Peripherin was demonstrated in all of the rectal well-differentiated endocrine neoplasms without metastases (12/12 cases), but was absent from some of the well-differentiated endocrine neoplasms with metastases (3/5 cases). Constant expression of peripherin in rectal well-differentiated endocrine neoplasms without metastases (12/12) seems to reflect the phenotype of the subpopulation of epithelial cells confined to the fetal rectum. However, loss of its expression was observed in cases with metastases (3/5) and can be regarded as an additional parameter to predict the risk of metastasis in rectal well-differentiated endocrine neoplasms.

Computed tomography findings of pathologically proven pulmonary infarction associated with bronchogenic carcinoma are reported for two patients. In one case, the infarction was demonstrated as a well-defined pleura-based large nodule in the peripheral portion of the same lobe of the tumor. The nodule had a smooth, convex border and a linear strand from the apex of the lesion toward the hilum. The obstruction of the subsegmental pulmonary artery due to tumor invasion was considered the cause of pulmonary infarction. In the second case, the infarction was demonstrated as a rapidly appeared, pleura-based consolidation in the same lobe of the tumor with a blurred border. Obstruction of the pulmonary vein by a tumor might have played an important role in the development of the pulmonary infarction in association with a large pulmonary artery obstruction. We conclude that pulmonary infarction should be considered as a differential diagnosis when peripheral pulmonary nodules or masses are located in the same lobe as the primary cancer.

A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs.

Cells regulate the rate of protein synthesis during conditions of cell stress to adapt to environmental changes. However, the molecular interactions between signaling pathways controlling translation and the cellular response to stress remain to be elucidated. Here, we show that the expression of growth arrest and DNA damage protein 34 (GADD34) is induced by energy depletion and that the expression of this protein protects cells from apoptotic cell death. During conditions of cell stress, GADD34 forms a stable complex with tuberous sclerosis complex (TSC) 1/2, causes TSC2 dephosphorylation, and inhibits signaling by mammalian target of the rapamycin (mTOR). These findings demonstrate that crosstalk between GADD34 and the mTOR signaling pathways contributes to the response of the protein synthetic machinery to environmental stress. GADD34 may find clinical potential as a target drug for the treatment of mTOR-associated diseases.

Mucinous metaplasia rarely develops in the non-neoplastic skin or its appendages, and almost exclusively confined to the genitalia, palms and soles. Similarly, mucinous metaplasia is quite uncommon in the cutaneous neoplasms and only few cases of clear cell hidradenomas and squamous cell carcinomas with mucinous metaplasia have been reported in the literature. Here we report a new case of clear cell hidradenoma with mucinous metaplasia in the forehead. Our immunohistochemical analysis revealed MUC5AC in the mucinous metaplastic cells of this tumor as in the extramammary Paget's disease, and expression of this gastric foveolar epithelial mucin core protein in these two neoplastic conditions seem to related to their common apocrine origin.

RB1-inducible coiled-coil 1 (RB1CC1) is a novel tumor suppressor implicated in the regulation of RB1 expression. It is abundant in post-mitotic neuromuscular cells, which are matured and enlarged, but scarce in smaller leukocytes, indicating an association between RB1CC1 status and cell size. To clarify whether RB1CC1 is involved in cell size control, we investigated the contribution of RB1CC1 to the TSC-mTOR pathway, which plays an important role in the control through translational regulation. RNAi-mediated knockdown of RB1CC1 reduced the activation of mTOR and S6K as well as the size of HEK293 and C2C12 cells. Such knockdown also suppressed RB1 expression and the population of G1-phase cells. Exogenous expression of RB1CC1 maintained S6K activity and cell size, and decreased TSC1/hamartin contents under nutritionally starved conditions, which usually inhibit the mTOR-S6K pathway. Furthermore, RB1CC1 interfered with and degraded TSC1 through the ubiquitin-proteasomal pathway. A lentiviral RNAi for RB1CC1 reduced the size of mouse leg muscles. These findings suggest that RB1CC1 is required to maintain both RB1 expression and mTOR activity. The activity of mTOR was supported by RB1CC1 through TSC1 degradation. RB1CC1 preserved cell size without cell cycle progression especially in neuromuscular tissues, and the abundance contributed to the non-proliferating enlarged cell phenotype.

We previously reported that MUC2 is a useful marker in the detection of lymph node micrometastasis (LMM) in gastric cancer. To improve the detection rate, we focused on a TFF1 gene. We used the duplex reverse transcriptase-polymerase chain reaction (RT-PCR) method with MUC2 and TFF1 genes to detect LMM in histologically node negative (pN0) early gastric cancer (EGC) and evaluated their effectiveness. A total of 310 lymph nodes from 33 patients with pN0 EGC were analyzed. All carcinoma specimens were positive for MUC2 and/or TFF1. The positive rate of TFF1 was significantly higher than MUC2 in the undifferentiated carcinoma specimens (p=0.002). The detection rate of duplex RT-PCR with MUC2 and TFF1 was higher than that of MUC2 or TFF1 alone. In mucosal cancer, 7 cases were positive for duplex RT-PCR. Of these 7 cases, 3 were MUC2-positive/TFF1-negative while 4 were MUC2-negative/TFF1-positive. LMMs were not detected in elevated-type primary mucosal cancers with a 20-30-mm diameter. The duplex RT-PCR assay with both MUC2 and TFF1 provides a higher LMM detection rate than either MUC2 or TFF1 alone, especially in mucosal gastric cancer. LMM detected in this manner may prove useful in broadening the indications for endoscopic mucosal resection in elevated-type cancer.

Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

We have analyzed extracellular matrix(ECM) of a case of pulmonary epithelioid hemangioendothelioma (PEH). Type IV collagen and laminin were existed in the ECM and were condensed around the tumor cell nests in meshwork pattern. Elastica-van Gieson stain revealed elastic fibers in this meshwork. These findings suggested that enhanced basement membrane protein synthesis in PEH seems to be responsible for the accumulation of abundant ECM. Analysis of the ECM seems to be quite useful for the differential diagnosis of this tumor.

RB1-inducible coiled-coil 1 (RB1CC1) is a novel molecule implicated in the regulation of RB1 (retinoblastoma 1) expression. However, information about the RB1CC1 gene is limited and its function remains somewhat obscure. The present study analyzes the expression and promoter activities of RB1CC1 in developing murine and human tissues. Rb1cc1 was abundantly expressed from an early stage of the mouse embryo throughout development. Immunohistochemical analyses revealed that Rb1cc1 was ubiquitous in the mouse, rather than in the human embryo, especially in the musculoskeletal system, heart and neural tissues. Promoter activity was highest in a region located about 300 bp immediately upstream of exon 1 in both the mouse and human RB1CC1 genes, suggesting that this region is a core promoter. The promoter activity of RB1CC1 was generally higher in mice than in humans, and suppressive with intron 1, especially in humans. These results suggested that more Rb1cc1 is expressed throughout developing murine than in human tissues, and that RB1CC1 expression is controlled more stringently by modification at intron 1 in humans than in mice.

It is well known that tumors originating from Schwann cells often demonstrate degeneration, such as myxoid areas in Schwannoma (Antoni B) and granular cell tumors. However, the mechanism has never been understood in detail. Recruitment of circulating macrophages plays a role in degeneration, however, the factors leading to that process are not well known. Macrophage inflammatory protein-1alpha (MIP-1alpha), which belongs to the C-C family of chemokines, is thought to be involved in the recruitment of inflammatory cells and might play a role in the degenerative change of Schwann cell tumors. To elucidate the role of MIP-1alpha in such conditions, we employed immunohistochemistry and in situ hybridization analyses. Strongly positive staining of MIP-1alpha was revealed in the myxoid areas of tested tumors and in situ hybridization detected the existence of MIP-1alpha mRNA in some of the tumor cells. These results suggest that MIP-1alpha produced from tumorigenic cells plays a role in the auto-degenerative process of Schwann cell tumors. Furthermore, various levels of MIP-1alpha expression in these tumors were implicated to be correlated with histological variations.

Multidrug resistance (MDR) to anticancer agents is a major barrier to the successful treatment of human osteosarcomas. Current understanding of the genes that contribute to the features of MDR is limited, and the mechanisms remain unclear. Here we applied differential display reverse transcription-polymerase chain reaction (DDRT-PCR) to parental and MDR-variants of U-2 OS human osteosarcoma cells, to clarify the genes involved in the MDR cells, and identified five candidate genes. These are BCRP (breast cancer resistance protein) encoding a transmembrane efflux pump; RB1CC1 (RB1-inducible coiled-coil 1), a tumor suppressor regulating RB1 (retinoblastoma 1) expression; a novel transcriptional variant of dUTPase; SSR2 (beta-signal sequence receptor), which is associated with protein translocation across ER membrane; and HSP105 encoding high molecular mass heat shock proteins. Molecular and biological characterization of these genes will yield further insight into the features between MDR and tumor progression in human osteosarcomas.

Background Intramuscular lipoma is a relatively common benign neoplasm that is occasionally described as an infiltrating lipoma. Typical benign tumors show a clear margin, however, the infiltrative growth pattern of this lipoma mimics that of a malignant tumor. Although its growth has an effect on muscle bundles and it is known to never metastasize, the mechanism of infiltrative growth is not well understood. Previously, little attention has been paid to pathogenic features of muscle fibers around an intramuscular lipoma. Methods In the present study, we focused on pathologic changes of the surrounding skeletal muscles especially to the degenerative features of involving muscular types, and evaluate the role of type-selective muscular degeneration for the infiltrative growth of intramuscular lipomas. Following a review of the medical records in our institute, 17 lesions containing muscle tissues in their specimens (15 infiltrating lipomas, 2 well-circumscribed lipomas) were analyzed immunohistochemically. The tumor from the most recent case was also subjected to ultrastructural analysis. Two cases of the traumatic muscle damage were also evaluated as the control experiments. Results These analyses revealed type-selective muscle involution in 11 of 17 intramuscular lipomas and in 10 of 11 of the infiltrative type, with an involving pattern that resembled that of a neurogenic or myogenic disorder. Immunoreactivity to cathepsin-D, a lysosomal catabolic enzyme, was increased in the involved muscle fibers. Subsarcolemmal vacuoles in the muscle fibers of the peripheral areas were also positive for cathepsin-D, while degenerative findings were not visually apparent in these areas. Ultrastructural analysis revealed degenerative changes in those fibers. Neither positive staining for cathepsin-D nor type-selective atrophy was detected in the sections of traumatic muscle damage. Conclusions Our findings suggest that type-selective muscular degeneration and endomysial fatty growth as a result of atrophy may modulate the infiltrating growth characteristic of intramuscular lipoma.

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.

We report a case of extraventricular ependymoma arising in a 50-year-old woman that took an aggressive clinical course with recurrence three times. The initial tumor was a well-circumscribed nodule in the right temporal white matter measuring 2 cm in diameter. It showed variegated histological findings mimicking metastatic adenocarcinoma: an epithelioid arrangement of highly pleomorphic cells with pseudopapillary structures and perivascular pseudorosettes, and bizarre multinucleated giant cells with occasional emperiporesis surrounded by abundant mononuclear inflammatory cells, as well as a focal small area of conventional ependymoma. Emperiporesis and abundant mononuclear cell infiltration were not previously described in an ependymoma. The recurrent tumors predominantly showed an epithelioid pattern with frequent formation of astroblastoma-like pseudopapillary structures. Neoplastic cells were markedly atypical and had characteristic intracytoplasmic eosinophilic inclusion bodies. Much of the cells in both the initial and recurrent tumors showed a positive immunostaining for glial fibrillary acidic protein (GFAP) with accentuation to the cytoplasmic processes of the pseudorosettes and pseudopapillary structures. Epithelial membrane antigen (EMA) highlighted the epithelial differentiation of the tumor cells, while cytokeratin was completely negative. Although this tumor might be classified to at least WHO grade III from the histology and aggressive behavior, the exact grading is still controversial because of the rarity of such cases.

Oxidative stress, IL-1alpha, and IL-8 are known to contribute to mucosal inflammation of the gastrointestinal tract. We examined the IL-8 response after brief exposure to hydrogen peroxide induced oxidative stress in CaCo-2 cells (a human colon carcinoma cell line) and in human intestinal epithelial cells. In addition, we examined whether exposure to oxidative stress, followed by IL-1alpha, could modulate IL-8 production. A transient up-regulation of IL-8 mRNA expression was observed after hydrogen peroxide treatment. Hydrogen peroxide induced oxidative stress was also observed to promote IL-8 secretion. Exposure to hydrogen peroxide, followed by IL-1alpha, enhanced IL-8 production over that achieved with IL-1alpha alone. Thus, oxidative stress and IL-1alpha were observed to cooperatively enhance IL-8 production.

Collagenous gastritis, a counterpart of collagenous colitis, is a rare disorder with less than 20 cases reported in the literature. A case of collagenous gastritis in a Japanese woman in her early 20s who had been receiving treatment for atopic dermatitis and bronchial asthma is reported. The patient complained of repeated epigastric pain, and endoscopy revealed multifocal atrophic areas and scars in the gastric body. Biopsy specimens showed a thickened eosinophilic band-like structure with entrapped capillaries approximately 30-70 micro m thick beneath the surface epithelium. It was regarded as a collagen band because it was positive on Azan staining but negative on amyloid staining. This finding was accompanied by marked infiltration of mononuclear cells and eosinophils in the lamina propria; however, no evidence of lymphocytic gastritis was found. Helicobacter pylori infection was not detected and inflammatory cell infiltration was minimal in the mucosa without the collagen band. Immunohistochemical analysis revealed that the band was positive for type III and type VI collagen. The size of the collagen band did not change for 2 years. These findings suggest that subepithelial collagen deposition was due to an abnormal local immune response based on generalized allergic disorder.

RB1-inducible coiled-coil 1 (RB1CC1) is a nuclear DNA-binding protein that can induce RB1 (retinoblastoma 1) expression. RB1CC1 is abundantly expressed in human musculoskeletal and cultured osteosarcoma cells. The present study analyzed the expression of RB1CC1 and RB1 in osteosarcoma cells and in musculoskeletal cells of human embryos to evaluate the contribution of both genes to the maturational process of musculoskeletal cells. The amount of RB1CC1 message was closely related to RB1 expression in various osteosarcoma cell lines. RB1CC1 expression was difficult to detect in immature proliferating chondroblasts or myogenic cells in human embryos, but became obvious and prominent concomitantly with the maturation of osteocytes, chondrocytes, and skeletal muscle cells. RB1CC1 expression in these musculoskeletal cells increased with RB1 expression, which is linked to the terminal differentiation of many tissues and cells. In addition, the introduction of wild-type RB1CC1 decreased the formation of macroscopic colonies in the cell growth assay. Accordingly, both RB1CC1 and RB1 genes preferentially co-expressed and contributed to the maturation of human embryonic musculoskeletal cells, and may regulate the proliferative activity and maturation of tumor cells derived from these tissues.

RB1CC1 ( RB1 -inducible C oiled- C oil 1 ), a putative transcription factor implicated in the regulation of RB1 (retinoblastoma 1) expression, was recently identified in a screen for genes involved in multi-drug resistance to anticancer agents. Information about the RB1CC1 gene is limited, however, and its biological function is not determined. Here we report the isolation, characterization and mapping of the mouse RB1CC1 gene (Rb1cc1), together with further characterization of the human RB1CC1 gene. Mouse Rb1cc1 encodes 1588 amino acids, sharing 89% identity and key sequence motifs with its human counterpart. Rb1cc1 is expressed abundantly in heart and testis, with lower levels detected in lung and spleen. Immunohistochemical analysis revealed the Rb1cc1 and Rb1 proteins are co-localized in the cell nuclei of NIH3T3-3 cell and various mouse tissues. The human and mouse RB1CC1 genes, both of which contain 24 exons, span 74 kb on chromosome 8q11.2 and 57 kb on chromosome 1A2–4, respectively. Conserved sequence motifs and nuclear localization suggest that the RB1CC1 proteins function as transcription factors.

The protein RB1CC1 (retinoblastoma 1 (RB1)-inducible coiled-coil 1) has been identified as a key regulator of the tumor-suppressor gene RB1 (ref. 1). RB1CC1 is localized in the nucleus and has been proposed to be a transcription factor because of its nuclear localization signal, leucine zipper motif and coiled-coil structure. The gene RB1CC1 is localized to a region of chromosome 8q11 (ref. 2) containing several loci of putative tumor-suppressor genes; however, its role in human cancers remains to be determined. Here we report that 20% (7 of 35) of primary breast cancers examined contained mutations in RB1CC1, including nine large interstitial deletions predicted to yield markedly truncated RB1CC1 proteins. Wildtype RB1CC1 and RB1 were absent or significantly less abundant than normal in the seven cancers with mutations in RB1CC1, but were abundant in cancers without such mutations. In all seven cancers, both RB1CC1 alleles were inactivated; two showed compound heterozygous deletions. Thus, RB1CC1 is frequently mutated in breast cancer and shows characteristics of a classical tumor-suppressor gene.

Chordoma is a relatively rare malignant bone tumor thought to arise from the remnants of the fetal notochord. Chordomas express epithelial cell markers such as cytokeratin and epithelial membrane antigen (EMA), which strongly suggests that the tumor cells grow via the mechanism of epithelial characterized cell-cell interactions. However, there are no known reports that have studied epithelial characterized cell-adhesion molecules such as E-cadherin or epithelial cell adhesion molecule (Ep-CAM) in chordomas. An immunohistochemical investigation was performed in seven cases of chordoma to determine the expression of pan-cytokeratin, Ep-CAM, and E-cadherin. Histological specimens showed the typical appearance of conventional chordoma but for two cases of chondroid chordoma. Cytokeratin was constantly expressed in conventional chordomas, but it was detected among a few cells with physaliphorous appearance in chondroid chordoma cases. Although no Ep-CAM expression was noted, E-cadherin was detected in most chordoma cells irrespective of histological subtypes. The expression of E-cadherin was negative among chondrosarcoma cells in this study as previously reported, and thus constant E-cadherin expression of chordoma cells suggests a role as a useful diagnostic marker to distinguish chondroid chordoma from chondrosarcoma. Furthermore, we speculate that E-cadherin may play a role in tumor cell adhesion and is also involved with histological and clinical features in chordomas.

We have evaluated the accuracy of high sensitive CRP assay method using evanescent wave Immunoassy system(Evanet 20) and significance of this assay on the early detection of infectious diseases in newborn babies. In this assay system, prozone phenomenon was not detected up to 40 mg/dl. The reproducibility of this assay was quite good and the intra run CV value of the same sample was less than 5% for the assay of serum, plasma and whole blood. There was a high correlation between the CRP values in the serum and plasma(r = 0.98, regression formula y = 0.89x + 4.07). Similarly, the values in whole blood and serum samples were quite well correlated(r = 0.98, regression formula y = 0.91x - 6.75). Various humoral elements such as bilirubin, hemoglobin and Chyl did not significantly influence this assay method. A slight increase in blood CRP was clearly demonstrated in the early phase of infectious diseases of newborn babies and monitoring of CRP by this assay system seemed to be quite useful to detect the early phase of infectious diseases in newborn babies. This assay system requires only a small quantity of whole blood to perform quantitative analysis of very small amounts of other substances. Accordingly, this assay system seems to be quite effective for monitoring minute increases in various proteinaceous blood components in emergent laboratory examination or POCT.

e15063 Background: We have recently shown that viable cancer cells spilled into peritoneal cavity during curative gastric cancer (GC) surgery more frequently in cases with advanced tumor invasion a...

Multidrug resistance to anti-cancer agents (MDR) is a major barrier to successful cancer treatment. Current knowledge about genes that contribute to MDR is limited, however, and its mechanisms remain unclear. To identify genes involved in MDR, we performed differential display analysis and isolated a novel human gene, RB1CC1 (RBI-inducible Coiled-Coil 1). The 6.6-kb RB1CC1 cDNA encodes a putative 1594-amino-acid protein that contains a nuclear localization signal, a leucine zipper motif and a coiled-coil structure. Western blot analysis and immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously expressed RB1CC1 protein localized to the nucleus. In MDR variants of human osteosarcoma cells, RB1CC1 expression increased in response to doxorubicin-induced cytotoxic stress and remained elevated for the duration of drug treatment. RB1CC1 expression levels correlated closely with those of RB1 (retinoblastoma 1) in cancer cell lines as well as in various normal human tissues. Moreover, introduction of wild-type RB1CC1 significantly induced RB1 expression in human leukemic cells. These data suggest that RB1CC1 may be a key regulator of RB1 gene expression.

A 44-year-old woman was admitted to the authors' institution for evaluation of two masses in the right forefoot. Standard radiographs showed foci of calcification within the mass. Magnetic resonance imaging and macroscopic findings during surgery revealed the lesion was composed mainly of two different portions: dorsal cystic masses and a solid mass in the plantar side of the fifth metatarsal head. Histologic and immunohistochemical examinations showed that the former was an intermetatarsophalangeal bursitis induced by keratinous material, whereas the latter was a ruptured epidermal cyst. To the best of the authors' knowledge, the current case is the first report of intermetatarsophalangeal bursitis caused by an untreated epidermal cyst.