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Objective Recent studies have suggested that infectious organisms play a role in vascular diseases. In this study, to explore a possible link between oral infection and Buerger disease, we investigated whether oral (periodontal) bacteria were present in occluded arteries removed from patients with characteristic Buerger disease. Methods Fourteen male patients with a smoking history who had developed characteristics of Buerger disease before the age of 50 years were included in this study. Occluded arteries, including superficial femoral (n = 4), popliteal (n = 2), anterior tibial (n = 4), and posterior tibial (n = 4) arteries, were removed and studied. A periodontist performed a periodontal examination on each patient and collected dental plaque and saliva samples from them at the same time. The polymerase chain reaction method was applied to detect whether seven species of periodontal bacteria— Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella intermedia , and Prevotella nigrescens — were present in the occluded arteries and oral samples. In addition, arterial specimens from seven control patients were examined by polymerase chain reaction analysis. Results DNA of oral bacteria was detected in 13 of 14 arterial samples and all oral samples of patients with Buerger disease. Treponema denticola was found in 12 arterial and all oral samples. Campylobacter rectus, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis , and Prevotella nigrescens were found in 14% to 43% of the arterial samples and 71% to 100% of the oral samples. A pathologic examination revealed that arterial specimens showed the characteristics of an intermediate-chronic-stage or chronic-stage lesion of Buerger disease. All 14 patients with Buerger disease had moderate to severe periodontitis. None of the control arterial samples was positive for periodontal bacteria. Conclusions This is the first study to identify oral microorganisms in the lesions of Buerger disease. Our findings suggest a possible etiologic link between Buerger disease and chronic infections such as oral bacterial infections.

Members of the inhibitor of apoptosis protein (IAP) family, including survivin, have been reported to be expressed in many tumors. However, their expression in esophageal cancer has not been clarified completely. We investigated the expression of mRNA for IAP family proteins in samples from esophageal cancers and their adjacent normal mucosa tissues by real-time quantitative RT-PCR. The survivin expression in esophageal cancer was significantly higher than that in normal mucosa (P < 0.05). Other IAP family proteins including cIAP1, cIAP2, NAIP and XIAP tended to show stronger expression in cancer tissue than normal mucosa, although the differences were not significant. As to the histological type of tumor, poorly differentiated squamous cell carcinomas exhibited significantly higher level of expression than well-differentiated carcinomas (P < 0.05). The proportion of apoptotic cells of cancer tissue inversely correlated with the intensity of survivin expression (P < 0.05). Immunohistochemical staining demonstrated cytoplasmic as well as nuclear expression of survivin in esophageal cancer, and further, in situ hybridization analysis demonstrated cytoplasmic expression of mRNA for survivin. The results suggest that the expression of IAP family proteins, especially survivin, may be associated with the biological character of esophageal cancer, such as apoptosis.

Hypoxia is a stress that causes alterations in signal transduction and gene instability. In the cancer microenvironment, hypoxia plays a significant role in forming a tumor phenotype and tumor progression. We aimed to identify the genes upregulated by hypoxia in human breast cancer cell lines, a hormone-dependent MCF-7 and a hormone-independent MDA-MB-231, using microarray analysis. These cells were exposed to two oxygen concentrations such as 21% and 1% in a time-course. Out of 12625 genes, 26 genes were identified as commonly upregulated in both MCF-7 and MDA-MB-231 cells. Some of these genes were already reported as hypoxia-related, but some of those were identified newly. These commonly upregulated genes between hormone-dependent and hormone-independent cells would be a clue to study hypoxia-related events and to explore the novel therapeutic targets in human breast cancer.

Laparoscopic findings of nine patients with chronic schistosomiasis japonica were analyzed and compared to hepatic ultrasonograms, computed tomography (CT) scans and histological findings from the same patients. In all nine patients laparoscopy revealed yellowish, small speckles, approximately 50 microm in diameter, sparse or clustered over the liver surface, which were later found to represent subcapsular calcified ova of Schistosoma japonicum. While the liver surface was almost smooth in mild schistosomiasis, multiple whitish markings and irregular, relatively wide, groove-like septums were seen in more advanced cases. In severe schistosomiasis block-like formations of variable size, separated by groove-like depressions, made the liver surface appear like a tortoise shell. In moderate or severe schistosomiasis ultrasonography revealed spotted high echoes and CT scans demonstrated network patterns and lineal calcified spots. The liver surface of chronic schistosomiasis japonica without re-infection appeared stable without change over time but with a tendency to improve. Hepatocellular carcinoma was initially recorded in two of the nine patients and follow-up revealed a further two with the same diagnosis. However, all these four cases also had chronic hepatitis C (HCV). Hepatocellular carcinoma was not detected in patients without viral hepatitis, indicating that hepatic viral infection is more important than schistosomiasis in promoting the development of hepatocellular carcinoma.

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.

Pancreatic involvement in primary sclerosing cholangitis (PSC) is an extremely rare condition, and its pathologic features are poorly documented. We report two cases of an unusual lymphoplasmacytic sclerosing inflammatory disease involving the total pancreas, common bile duct, gallbladder, and, in one patient, the lip. Two elderly men presented with waxing and waning obstructive jaundice, and exhibited radiologic and ultrasonographic findings highly suggestive of pancreatic carcinoma. Gross appearance of the pancreas showed firm and mass-like enlargement with regional lymph node swelling. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Similar inflammatory processes involved the bile duct and the gallbladder. Lymphoplasmacytic sclerosing pancreatitis with cholangitis is thought to be a more appropriate term for this condition, of which a similar lesion has been previously noted in a single case of "PSC involving pancreas". Differences in age, radiologic appearance, and the negative history of ulcerative colitis exist, but the two cases in this study could be considered as a variant of PSC extensively involving pancreas, which can readily be mistaken for pancreatic carcinoma.

An immunohistochemical and clinicopathologic analysis of glomerular alterations was carried out in 20 autopsy cases with obstructive jaundice. The 20 cases without clinical nephritis had primary carcinoma of various locations, including the stomach, rectum, pancreas, and biliary tract. Mesangial IgA deposition was present on immunofluorescence staining in four cases, IgG in two cases, IgM in five cases, and C3 in four cases. Glomerular polymeric IgA containing A1, A2, and J chain was considered to originate from the gastrointestinal tract. All immunofluorescence-positive cases except one had electron-dense deposits in mesangial regions. These findings suggest that glomerular IgA deposition develops in a handful of patients suffering from obstructive jaundice, presumably due to the passive trapping of circulating immune complexes. Furthermore, glomerular IgA deposition in patients with obstructive jaundice is not influenced by duration or intensity of jaundice, and it unlikely induces clinical nephritis.

Clinicopathologic and immunohistochemical analyses of the kidneys in 30 autopsy cases of liver cirrhosis of different types revealed glomerular lesions in 27 cases. Clinical nephritis was present in three cases. Characteristic diffuse mesangial proliferation with focal mesangial interposition and/or subendothelial deposits were present. Glomerular immunoglobulin deposition was observed in several cases, IgM in 23 cases, IgG in five, and IgA in 17; the latter were predominantly IgA1. Secretory component binding was found in 11 of the 17 cases with IgA deposits (65 per cent). Liver weight was related to IgA deposition ( P ∼0.05), and the volume of ascitic fluid was significantly correlated ( P

The developmental sequence of human pancreatic secretory proteins has not previously been studied in detail. We applied immunohistochemistry to study 20 fetal and neonatal pancreas' (8th to 39th gestational weeks) using antisera against the following pancreatic secretory proteins: pancreatic secretory trypsin inhibitor (PSTI), serine proteinases (trypsin, chymotrypsin, and elastase I), and amylase. PSTI was first detected in developing buds of the pancreas during the 8th gestational week, and proteinases were observed in acinar cells during the 14th week of gestation. Immunoreactivity for both PSTI and proteinases was found in most acinar cells soon after their appearance. Immunoreactivity for amylase could not be detected in fetal or neonatal pancreas tissue. PSTI was also found in developing islets during the 14th gestational week, but the number of immunoreactive cells had decreased by term. Cells positive for serine proteinases were occasionally in contact with islets in second-trimester fetuses. In discussing these results, we give particular attention to the nonparallel appearance of secretory products in the fetal pancreas, and the significance of cells immunoreactive for secretory proteins in endocrine islets.