A unique autopsy case of ascending aortic dissection caused by giant cell arteritis without drug therapy.

Giant cell arteritis is a granulomatous inflammation of large and medium-sized arteries, occurring predominantly in older women. In this case, a 76-year-old woman was hospitalized for examination because of a high C-reactive protein (CRP) level, but nothing remarkable was found on thoracicoabdominal computed tomography (CT) or head magnetic resonanse imaging (MRI). On the 46th day from the first visit, she died suddenly due to cardiac tamponade. On pathological autopsy, we found the cause of death to be acute aortic dissection (Stanford type A) due to giant cell arteritis occurred in the ascending aorta. Histologically, granulomatous vasculitis with giant cells was recognized in the ascending aorta, thoracic descending aorta and abdominal aorta and their branches. Interestingly, similar granulomatous vasculitis was also found in the medium and small vessels of other plural organs, including the heart, liver, uterine corpus, and its appendages. To our knowledge, giant cell arteritis with multiple-organ granulomatous changes has not been reported before. We herein reported a unique autopsy case of giant cell arteritis in a patient not treated with medication.

Cytokeratin immunohistochemistry improves interobserver variability between unskilled pathologists in the evaluation of tumor budding in T1 colorectal cancer.

Tumor budding is a major risk factor for T1 colorectal cancer. Quality control of the pathological diagnosis of budding is crucial, irrespective of the pathologist's experience. This study examines the interobserver variability according to pathologists' experience and evaluates the influence of cytokeratin (CK) immunostaining in the assessment of budding. Hematoxylin-eosin (HE) and CK-immunostained slides of 40 cases with T1 primary colorectal cancer were examined. Budding grades were individually evaluated by 12 pathologists who we categorized into three groups by their experience (expert, with >10 years of experience (n = 4), senior, with 5-10 years (n = 4), and junior, < 5 years (n = 4)). The results revealed a tendency for the more experienced pathologists to assign higher budding grades compared to the less-experienced pathologists. In the junior group, the interobserver variability obtained with HE slides was poor, but it was markedly improved in the evaluation using CK-immunostained slides. The benefit of CK immunostaining was only slight in the expert group. CK immunostaining would be useful when a pathologist is not experienced enough or does not have enough confidence in the assessment of budding.

Cross-reactivity between major IgE core epitopes on Cry j 2 allergen of Japanese cedar pollen and relevant sequences on Cha o 2 allergen of Japanese cypress pollen.

BACKGROUND: Cry j 2 and Cha o 2 are major allergens in Japanese cedar (Cryptomeria japonica; CJ) and Japanese cypress (Chamaecyparis obtusa; CO) pollen, respectively. Here, we assessed the epitopes related to the cross-reactivity between Cry j 2 and Cha o 2 using in vitro analyses. METHODS: Peptides were synthesized based on Cry j 2 sequential epitopes and relevant Cha o 2 amino acid sequences. Four representative monoclonal antibodies (mAbs) against Cry j 2 were used according to their epitope recognitions. Serum samples were collected from 31 patients with CJ pollinosis. To investigate cross-reactivity between Cry j 2 and Cha o 2, ELISA and inhibition ELISA were performed with mAbs and sera from patients with CJ pollinosis. RESULTS: Two of four mAbs had reactivity to both Cry j 2 and Cha o 2. Of these two mAbs, one mAb (T27) recognized the amino acid sequence (169)KVVNGRTV(176) on Cha o 2. This is related to the core epitope (169)KWVNGREI(176) on Cry j 2, which is an important IgE epitope. In addition, we found that these correlative sequences and purified allergens showed cross-reactivity between Cry j 2 and Cha o 2 in IgE of CJ patients. CONCLUSIONS: We demonstrated the importance of (169)KVVNGRTV(176) in Cha o 2 for cross-reactivity with the Cry j 2 epitope (169)KWVNGREI(176), which plays an important role in allergenicity in CJ pollinosis. Our results are useful for the development of safer and more efficient therapeutic strategies for the treatment of CJ and CO pollen allergies.

Fatal convexity and interhemispheric acute subdural hematoma from a falx meningioma: A case report.

Background: Hemorrhagic meningiomas are rare. We report a rare case of nontraumatic convexity and interhemispheric acute subdural hematoma (ASDH) caused by a falx meningioma. Case Description: An 84-year-old woman with a history of atrial fibrillation and hypertension who was taking warfarin presented to our emergency department with a sudden disorder of consciousness. The patient had no traumatic events associated with her symptoms. Computed tomography (CT) revealed right convexity and interhemispheric ASDH, mass lesions in the left frontal lobes, and brain herniation. Contrast-enhanced CT revealed vascular structures within the mass lesion. CT angiography (CTA) revealed no aneurysm or arteriovenous malformation, and the venous phase revealed occlusion in the anterior portion of the superior sagittal sinus. The patient had her right convexity and interhemispheric ASDH removed endoscopically. A mass lesion located on the falx, which was easily bleeding, soft, and suctionable, was immediately detected. Histopathological examination revealed fibrous meningioma, a benign meningioma of the World Health Organization grade 1. Despite undergoing aggressive treatment, the patient's general condition deteriorated. Conclusion: Hemorrhagic meningiomas can easily be missed with plain CT, and the enhancement effect of CTA and tumor shadow on digital subtraction angiography may not be observed during the acute phase. Surgery for nontraumatic ASDH should be performed considering the possibility that a meningioma causes it.

Analysis of conformational and sequential IgE epitopes on the major allergen Cry j 2 of Japanese cedar (Cryptomeria japonica) pollen in humans by using monoclonal antibodies for Cry j 2.

PURPOSE: Japanese cedar (Cryptomeria japonica; CJ) pollinosis is a type I allergy induced by CJ pollen, and Cry j 2 is one of the major allergens in this pollen. In a previous study, we analyzed IgE epitopes on Cry j 2 in humans by using synthetic peptides. The main purpose of this study was to identify B-cell epitopes on Cry j 2 in patients with CJ pollinosis by using monoclonal antibodies (mAbs) for Cry j 2. METHODS: We used ELISA with mAbs for the epitope analysis. Sera samples were collected from 80 patients with CJ pollinosis, and allergenic epitopes for mAbs and human IgE were identified using ELISA with synthetic peptides. The importance of the epitopes for human IgE was analyzed using an inhibition ELISA. RESULTS: Four independent epitopes (epitope #1, #2, #3, and #4) were identified on Cry j 2 with the use of mAbs. Epitope #3 and #4, corresponding to peptides No. 25 and No. 33, respectively, were newly determined as epitopes for mAbs and human IgE. Inhibition ELISA showed that not only epitope #2 (sequential) but epitope #1 (conformational) may play an important role in the CJ pollinosis. CONCLUSIONS: Our results revealed 4 epitopes, including two new ones, on Cry j 2. We also found that inhibition ELISA with appropriate mAbs could be a viable method of evaluating the importance of the conformational and sequential epitopes for human IgE. These results are beneficial for the development of safer and more efficient therapeutic strategies for treating CJ pollinosis.

CT-gastrography for early gastric cancer visualized by wall-carving technique using contrast-enhanced MDCT for portal phase.

OBJECTIVE: The wall-carving (WC) imaging technique is used to evaluate early gastric cancer using multidetector row computed tomography (MDCT) image data for only the arterial phase. Our purpose was to investigate if WC images derived from portal phase MDCT images can enhance the visualization of early gastric cancer. SUBJECTS AND METHODS: Fourteen consecutive patients (average age/age range (years) = 75.8/61 to 86; male/female = 9/5) were enrolled. They were diagnosed with early gastric cancer and underwent contrast-enhanced MDCT before treatment. WC images of the arterial and portal phases were created from images scanned by 64-detector-row MDCT 40 and 60 seconds after the initiation of the contrast material injection, respectively. The correlation between the detection rates of lesions in the WC images and pathological findings was investigated. RESULTS: Totals of 71.4% (10/14) of arterial phase WC images and 71.4% (10/14) of portal phase WC images showed lesions. The imaging ability improved to 85.7% (12/14) when the two sets of images were combined. Well-differentiated adenocarcinomas tended to be visualized better in WC images of any phases. CONCLUSION: WC is an excellent image analysis technique for visualizing early gastric cancer lesions. The depiction rates were improved by using a combination of arterial and portal WC images. The scan timing after the contrast material injection should be carefully investigated to improve the detection rate of lesions.

Metachronous aortic aneurysms due to sarcoidosis.

A 62-year-old male developed metachronous aortic aneurysms at different locations over an interval of one year and three months. He was diagnosed to have sarcoid aneurysms due to the presence of noncaseating epithelioid granulomas in the aortic wall and lymph nodes. The patient was treated with steroids, but his sarcoidosis progressed gradually and extended into other major organs, and the lungs and heart were clinically determined to have been involved by sarcoidosis. He died of cardiac tamponade four years after the first operation for an aortic aneurysm.

IgE sensitivity to Malassezia pachydermatis and mite allergens in dogs with atopic dermatitis.

In this study, dogs with atopic dermatitis were separated into non-food-induced atopic dermatitis (NFIAD) group (n = 15) and food-induced atopic dermatitis (FIAD) group (n = 37) based on an elimination diet test. IgE reactivity for crude Malassezia pachydermatis (M. pachydermatis) and house dust mites (HDM) allergen extracts was investigated in the two groups using fluorometric enzyme-linked immunosorbent assay (ELISA) and intradermal skin test (IDST). Nine (60%) of the 15 dogs in NFIAD group and 6 (16%) of the 37 dogs in FIAD group showed specific IgE for M. pachydermatis (Mann-Whitney U-test, P < 0.01). By immunoblotting analysis, the pooled serum samples from dogs with IgE for M. pachydermatis showed IgE reactivity for 50 kDa protein of M. pachydermatis. Twelve (80%) of the 15 dogs in NFIAD group and 8 (22%) of the 37 dogs in FIAD group showed specific IgE for HDM (Mann-Whitney U-test, P < 0.01). In addition, the dogs in NFIAD group significantly show a positive IDST to M. pachydermatis and HDM extracts compared with the dogs in FIAD group. The results suggest that dogs with NFIAD are at increased risk of becoming sensitized to the normal commensal organism M. pachydermatis compared with dogs with FIAD, perhaps co-sensitization occurred due to an HDM protease antigen's, Der f 1 and/or Der p 1, proteolytic activity related epidermal skin barrier defects. Treatment to limit skin colonization may thus be especially important in NFIAD.

Fumagillin inhibits colorectal cancer growth and metastasis in mice: in vivo and in vitro study of anti-angiogenesis.

Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation, but its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated. In this study, male severe combined immunodeficiency (SCID) mice were injected with colon cancer cells in the subcutis and then treated with Fumagillin and Cyclo (Arg-Gly-Asp-D-Phe-Val), an integrin alphavbeta(3) antagonist. The tumor weight, microvessel density (MVD), and number of pulmonary metastatic foci were examined. Gene expression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVEC). The Fumagillin-treated mice had smaller tumor mass, fewer pulmonary metastases, and lower MVD-CD105 levels than control animals. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVEC showed upregulation of 71 genes and downregulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion, and gene transcription. Quantitative real-time-polymerase chain reaction and western blotting showed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. This downregulation by Fumagillin may be involved in the anti-angiogenesis by Fumagillin. In conclusion, Fumagillin was found to suppress colorectal cancer growth and metastasis by suppressing angiogenesis.

CT-based mediastinal compartment classifications and differential diagnosis of mediastinal tumors.

Division of the mediastinum into compartments is used to help narrow down the differential diagnosis of mediastinal tumors, assess tumor growth, and plan biopsies and surgical procedures. There are several traditional mediastinal compartment classification systems based upon anatomical landmarks and lateral chest radiograph. Recently, the Japanese Association of Research of the Thymus (JART) and the International Thymic Malignancy Interest Group (ITMIG) proposed new mediastinal compartment classification systems based on transverse CT images. These CT-based classification systems are useful for more consistent and exact diagnosis of mediastinal tumors. In this article, we review these CT-based mediastinal compartment classifications in relation to the differential diagnosis of mediastinal tumors.

Pathological features of classical polyarteritis nodosa: analysis of 19 autopsy cases.

Classical polyarteritis nodosa (cPN) is a rare autoimmune disease featuring systemic inflammation of middle- and small-sized arteries. Because most of autopsy cases underwent clinical treatment, arterial fibrinoid necrosis, which is the most specific finding of cPN, is often obscure. The aim of this study was to seek morphological characteristics of the middle-sized arteries in autopsy cases of cPN, and to identify immunohistochemical markers for the diagnosis of cPN. Nineteen patients who had undergone autopsy with a diagnosis of cPN were enrolled. Twenty-one autopsy cases without cPN were examined as control group. Arterial fibrinoid necrosis in medium-sized arteries was observed in 8/19 autopsy cases. Elastica van Gieson staining showed an increased number of elastic fiber layers (P<0.0001) and greater distances between elastic fiber layers (P<0.0001) in the renal middle-sized arteries of the cPN group. These findings probably reflected the post-inflammatory remodeling process after necrotizing vasculitis. On immunohistochemical examination, the cPN group showed high matrix metalloproteinase-1 and tumor necrosis factor-α expressions and decreased smoothelin expression in the vascular wall compared to the control group. When uncertain or atypical autopsy cases of cPN are examined, these findings can help to make the pathological diagnosis of cPN.

A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies.

A 73-year-old Japanese woman was hospitalized for detailed examination of nausea, diarrhea and loss of appetite. Atypical erosion in the ileum was found on endoscopy. Biopsy of this erosion showed proliferation of cells containing numerous Russell bodies. Differential diagnoses considered were Russell body enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative small intestinal disease (IPSID) and mucosa-associated lymphoid tissue (MALT) lymphoma. The cells containing prominent Russell bodies showed diffuse positivity for CD79a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68. Russell bodies were diffusely positive for lambda light chain, but negative for kappa light chain, and immunoglobulin (Ig) G, IgA and IgM. Based on these findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were ruled out. As the tumor formed no mass lesions and was restricted to the gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation was finally diagnosed. The patient showed an unexpectedly aggressive clinical course. The number of atypical lymphocytes in peripheral blood gradually increased and T-prolymphocytic leukemia (T-PLL) emerged. The patient died of T-PLL 7 mo after admission. Autopsy was not permitted.

Mitotic count reflects prognosis of gallbladder cancer particularly among patients with T3 tumor.

The surgical strategy for gallbladder cancer (GBC) depends on the extent of the disease. Thus, the identification of useful prognostic markers exerting strong prognostic impact for each T stage would be beneficial in the development of rational therapeutic strategies. The purpose of this study was to identify useful prognostic markers of GBC for each T stage. CD8+ tumor-infiltrating lymphocytes (TIL), Ki-67 labeling index (LI), p53 nuclear expression and mitotic count (MC) were investigated as candidate prognostic markers. In total, 86 patients with invasive GBC were included. Of the prognostic markers examined, only MC showed a correlation with reduced survival (P=0.0383) in the univariate analysis of overall T stage. In the univariate analysis of T2 stage (n=31), only high p53 expression correlated with survival showing a positive correlation (P=0.0154). In the univariate analysis of T3 stage (n=40), the only factor showing a significant correlation with survival was MC (P=0.0113). Multivariate analysis, including N and M as factors, identified only MC as an independent prognostic factor in T3 stage GBC (P=0.0419). In conclusion, this study demonstrated the strong prognostic impact of MC in GBC, particularly in patients with T3 tumor.

Large-scale survey of adverse reactions to canine non-rabies combined vaccines in Japan.

Canine non-rabies combined vaccines are widely used to protect animals from infectious agents, and also play an important role in public health. We performed a large-scale survey to investigate vaccine-associated adverse events (VAAEs), including anaphylaxis, in Japan by distributing questionnaires on VAAEs to veterinary hospitals from April 1, 2006 through May 31, 2007. Valid responses were obtained for 57,300 vaccinated dogs at 573 animal hospitals; we obtained VAAEs information for last 100 vaccinated dogs in each veterinary hospital. We found that of the 57,300, 359 dogs showed VAAEs. Of the 359 dogs, death was observed in 1, anaphylaxis in 41, dermatological signs in 244, gastrointestinal signs in 160, and other signs in 106. Onset of VAAEs was mostly observed within 12h after vaccination (n=299, 83.3%). In this study, anaphylaxis events occurred within 60 min after vaccination, and about half of these events occurred within 5 min (n=19, 46.3%). Furthermore, where anaphylaxis was reported, additional information to support the diagnosis was obtained by reinvestigation. Our resurvey of dogs with anaphylaxis yielded responses on 31 dogs; 27 of these demonstrated collapse (87.1%), 24 demonstrated cyanosis (77.4%), and both signs occurred in 22 (71.0%). Higher rates of animal VAAEs, anaphylaxis, and death were found in Japan than in other countries. Further investigations, including survey studies, will be necessary to elucidate the interaction between death and vaccination and the risk factors for VAAEs, and thus develop safer vaccines. Moreover, it may also be necessary to continually update the data of VAAEs.

Analysis of Extrahepatic Multiple Primary Malignancies in Patients with Hepatocellular Carcinoma according to Viral Infection Status.

Previous studies have investigated extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC). However, its correlation with viral infection, such as hepatitis B virus (HBV) or hepatitis C virus (HCV), has not been examined. The aim of this study is to investigate the association between EHPM and hepatitis infection in HCC patients. A total of 412 patients who underwent surgical resection for primary HCC were enrolled. Viral infection was evaluated by serum HBV surface antigen (HBs Ag) and HCV antibody (HCV Ab). Sixty-eight (16.5%) patients had one or more EHPM. The most frequent EHPM was gastric cancer (n = 32) in this cohort. No statistical significance was observed in the distribution of viral infection and incidence of entire EHPM. However, HCV Ab, HBs Ag, and negative status for both were correlated with the frequency of gastric (P = 0.0194), urinary tract (P = 0.0067), and breast cancer (P = 0.0036), respectively. Infection of Helicobacter pylori was investigated by immunohistochemistry in gastric EHPM and resulted that 20 out of 21 analyzed cases were negative for Helicobacter pylori. Although it should be verified by well-designed large cohort studies, the current results suggested correlation between HCV infection and gastric cancer, HBV infection and urinary tract cancer and viral hepatitis-free status and breast cancer in HCC patients.

IgE reactivity to a Cry j 3, an allergen of Japanese cedar (Cryptomeria japonica) pollen in dogs with canine atopic dermatitis.

The present study investigated IgE reactivity to a new Cryptomeria japonica pollen allergen (Cry j 3) in dogs with atopic dermatitis by using a fluorometric ELISA. Serum samples from 15 dogs that showed IgE sensitivity to crude C. japonica pollen allergen by ELISA were tested for specific IgE to each allergen, individually. All 15 dogs had anti-Cry j 1 IgE, 6 (40%) had anti-Cry j 2 IgE, and 11 (73%) had anti-Cry j 3 IgE. Further, we found that these anti-Cry j 3 IgE reacted to Cry j 3 with immunoblotting analysis. These findings indicate that Cry j 3 may be a major allergen in dogs.

Endoglin (CD105) expression and angiogenesis status in small cell lung cancer.

It is well established that angiogenesis is crucial for tumor development and progression. Among the angiogenesis immunomarkers defined to date, endoglin (CD105) has been shown to be a useful marker of angiogenesis. To investigate the degree of angiogenesis status in small cell lung cancer (SCLC) tissue, we assessed 35 cases of SCLC at autopsy using immunohistochemical staining of CD31 and CD105. The intratumoral area, peritumoral area, and background pulmonary alveoli were then observed under low magnification, and the microvessel density (MVD) for each area was determined. The MVD-CD31 was the highest in the background alveoli, followed by the intratumoral and peritumoral areas. The MVD-CD105 was highest in the intratumoral area, followed by the peritumoral area and the background lung. The ratio of CD105/CD31 revealed that almost 78% of the intratumoral area, 63% of the peritumoral area, and 4.6% of the background lung alveoli were newly formed and expressed CD105. This result indicated that SCLC is predominantly supported by newly formed vessels that are generated by CD105-mediated angiogenesis. These findings suggest that anti-angiogenic therapy, especially CD105-targeting, may prove an effective form of SCLC treatment.

Primary gastrointestinal stromal tumor of the liver with PDGFRA gene mutation.

Gastrointestinal stromal tumor is a mesenchymal tumor with KIT or PDGFRA gene mutation, occurring primarily in the stomach and intestine and rarely outside the digestive tract. KIT-negative tumors with epithelioid cell morphology and PDGFRA mutation represent a minor subset of gastrointestinal stromal tumor. Here, we describe a case of gastrointestinal stromal tumor in the liver of a 70-year-old man. The tumor was shown to be completely limited within the liver by radiologic, intraoperative, and pathologic examinations. Histopathologically, the tumor showed epithelioid cell-type morphology and immunohistochemical expression of CD34 and protein kinase C theta but was negative for cytokeratin, EMA, S-100, and HMB-45. KIT protein expression was very faint, and we judged it as negative. Mutation analysis revealed the presence of PDGFRA gene mutation (V561D) at exon 12. These findings are essentially the same as those typically seen in ordinary KIT-negative epithelioid cell-type gastrointestinal stromal tumor of the digestive tract. Although KIT-negative gastrointestinal stromal tumor occurring outside the gastrointestinal tract is very rare, this entity should be considered as a potential primary hepatic neoplasm.

Endoglin (CD 105) is expressed on endothelial cells in the primary central nervous system lymphomas and correlates with survival.

Endoglin (CD105) is predominantly expressed on the cellular lineages within the vascular system and it is overexpressed on proliferating endothelial cells that participate in neoangiogenesis, with a weak or negative expression in the vascular endothelium of normal tissues. To investigate the correlation between the CD105 expression and possible prognostic markers or progression in the primary central nervous system lymphomas (PCNSLs), the present study assessed 26 cases of PCNSL by immunostaining for CD105 and CD34. Intratumoral microvessel density (IMVD) was determined in the hotspots and interfaces at a magnification of x200. According to the mean value, the patients were classified into lower-IMVD and higher-IMVD groups. When CD34 was used as a marker of angiogenesis, the survival rates of these two groups demonstrated no significant difference. In contrast, when CD105 was used as a marker of angiogenesis, the survival rate of the lower-IMVD group was significantly higher than that for the higher-IMVD group (P < 0.01). In the group of CD34-immunostained vessels, no difference was observed in IMVD between the hotspots and interfaces (P = 0.31). In the group with CD105-immunostained vessels, a greater IMVD was observed in the hotspots than in the interfaces (P < 0.01). These results suggested that the growth of PCNSLs was dependent on angiogenesis, that IMVD as determined by anti-CD105 monoclonal antibody was a reliable prognostic marker in PCNSLs, and that PCNSLs may therefore not require sufficient neoangiogenesis at the start of PCNSLs, however, it may instead require a higher rate of neoangiogenesis as they infiltrate and destroy the brain parenchyma.