A platelet activating factor receptor antagonist inhibits cytokine production in human whole blood by bacterial toxins and live bacteria

We previously reported that a platelet-activating factor receptor (PAFR) antagonist (TCV-309) suppressed lipopolysaccharide (LPS)-induced mortality and tumor necrosis factor (TNF) production in mice. However, the effect of TCV-309 on cytokine production induced by Staphylococcus enterotoxin B (SEB) or live bacteria has not been reported. In this study we investigated the effect of TCV-309 on cytokine production in human whole blood induced by LPS, SEB, and both Gram-positive and -negative bacteria. Human whole blood diluted 5:1 (980 microL) was placed in the wells of a 24-well plate. Ten microliters of LPS, SEB, Escherichia coli O18 K(+), or Staphylococcus aureus were added to each well. After incubation at 37 degrees C for 6 h, TNF, interleukin (IL)-6, and IL-8 in the culture medium were measured. TCV-309 did not affect the growth of either E. coli or S. aureus bacteria in the culture medium for the 6 h incubation. LPS, SEB, and both E. coli and S. aureus induced TNF, IL-6, and IL-8 in human whole blood. TCV-309 significantly inhibited the production of TNF, IL-6, and IL-8 induced by LPS, SEB, and bacteria. A PAFR antagonist suppressed cytokine production induced by LPS, SEB, and both Gram-positive and -negative bacteria in human whole blood. A PAFR plays an important role of producing proinflammatory cytokines induced by both toxins and live bacteria. IMPLICATIONS: The platelet-activating factor receptor plays an important role in producing proinflammatory cytokines induced by bacterial toxins, such as lipopolysaccharide,Staphylococcus enterotoxin B, and live Gram-positive and Gram-negative bacteria.     

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.     

Multiple extracranial metastases from a meningeal hemangiopericytoma and severe hypoglycemia: a case report

Extracranial multiple metastases from meningeal hemangiopericytoma have been reported only rarely. The authors describe the case of a 61-year-old woman, who was previously diagnosed as having primary meningeal hemangiopericytoma with its multiple metastases to the liver, lumbar spine, etc. and who suffered from a sudden attack of hypoglycemia. Considering the history of her present illness, this hypoglycemic shock was most likely brought on by the remarkable metastatic tumors to the liver. Recent literature pertinent to hypoglycemia suggests that insulin-like growth factor-II (IGF-II) produced by tumor is strongly suspected to be involved in the development of hypoglycemia.     

Multiple recurrences of cerebellar hemangioblastoma after 20 years from initial total removal of the tumor

Cerebellar hemangioblastoma develops alone or develops as part of von Hippel-Lindau disease. Moreover, multiple hemangioblastomas are found in 10-15%. It was reported that some hemangioblastomas recur with multiple recurrence in long time follow-up period. A 51 years old male was referred to our hospital because of headache and found a cerebellar tumor which was totally removed and diagnosed as hemangioblastoma pathologically. He presented no deficit after first surgery, but he did not come our hospital. In May 2000, he was referred to our hospital because of headache again and found five cerebellar tumors on MRI. Angiography showed markedly tumor stain. Retinal and spinal lesions were not seen. Two of five tumors was removed. The remaining three small tumors were received gamma knife surgery. In December 2000, because of cyst enlargement, one tumor was removed and the cyst was opened. In June 2001, he presented right hearing disturbance due to enlargement of cerebellar pontine angle tumor. The tumor was removed after tumor embolization, but hearing disturbance and slight dizziness remained. The remaining 5 mm tumor is followed.     

What basic surgical research brings to surgical clinics

In this article, author describes the present problems of surgical clinics and the importance of basic research by young surgeons to improve the clinical outcomes of surgery.     

Pineal cystic germinoma with syncytiotrophoblastic giant cells mimicking MR imaging findings of a pineal cyst

We report a case of precocious puberty in a 4-year-old boy. Contrast-enhanced T1-weighted MR imaging suggested a pineal cyst with enhancement of the slightly thickened wall and focal wall irregularity. Three-dimensional constructive interference in a steady-state imaging revealed a focal lobulation and a nodule-like area in the lesion. The lesion mimicking a pineal cyst proved to be a germinoma with syncytiotrophoblastic giant cells, on the basis of biopsy and tumor marker results.     

Transoral penetration of a half-split chopstick between the basion and the dens

A 6-year-old girl was admitted for transoral penetrating injury by a half-split chopstick. Subsequent CT imaging examinations showed that the chopstick had passed between the basion and the dens and reached the subarachnoid space just at the medulla oblongata. A sagittal reconstructed CT scan was useful for the evaluation of the injury. Imaging findings and their clinical relevance are discussed.     

External-beam radiation therapy for age-related macular degeneration: two years' follow-up results at a total dose of 20 Gy in 10 fractions

PURPOSE: The efficacy of external-beam radiation therapy (RT) was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration (ARMD). MATERIALS AND METHODS: Twenty-one eyes of 18 patients with occult or mixed-type ARMD received a total dose of 20 Gy of 6 MV X-rays in 10 fractions. The follow-up time was 24 months. Fifteen non-treated eyes of 13 patients who had been followed served as a control. RESULTS: In the RT group, visual acuity was improved in three eyes, maintained in 14 eyes, and worsened in four eyes. In the control group, it was not improved in any eyes, was maintained in six eyes, and worsened in nine eyes. The improved or maintained rate in visual acuity was 81% in the RT group and 40% in the control group (p=0.0342). In the RT group, fundoscopic and angiographic findings were improved in five eyes, unchanged in seven eyes, and worsened in nine eyes, while they were not improved in any eyes, unchanged in two eyes, and worsened in 13 eyes in the control group(p=0.0342). CONCLUSION: RT at a total dose of 20 Gy in 10 fractions is effective for ARMD for at least two years. RT may be effective treatment for occult or mixed-type ARMD compared with the classic type.