Insular component as a risk factor of thyroid carcinoma

Forty-four thyroid carcinomas with an Insular component (JC) were reviewed from 2457 tumors diagnosed as papillary (PC) or follicular carcinoma (FC). These tumors were classified as FC with an IC (FCIC; 30 cases) and PC with an IC (PCIC; 14 cases). Both tumors were composed of solid cell nests in some areas and had a tendency toward a characteristic nuclear size: FCIC had a small nucleus and PCIC contained a nucleus of an Intermediate type or a large nucleus similar to that of PC, although there were numerous tumors with an exceptional nuclear size. The mean age and tumor diameter were the highest and largest in FCIC, respectively, followed by PCIC. Among the 44 cases, 17 patients died of the disease, two were alive with the disease and 18 were alive without the disease. From 13 clinicopathological factors, the presence of an IC, age, non-encapsulation, tumor size, vascular invasion and necrosis were found to be independent variables for actual prognosis of FC and PC based on univariate analysis followed by multtvariate analysis. The results of the present study indicate that the presence of an IC is an independent aggressive prognostic factor for patients with PC and FC.     

A CASE OF GASTRIC CARCINOMA WITH MASSIVE EOSINOPHILS

This report describes a 67-year-old male with inoperable gastric cancer accompanied by marked tissue and peripheral eosinophilia without evidence of allergic disorders or parasitic infestation. Autopsy revealed an advanced gastric cancer of scirrhous type with metastases to pancreas, bone marrow, ileum, lungs, and lymph nodes. Excessive numbers of mature eosinophils were present in univolved bone marrow, liver and spleen as well as among the signet ring cell component of the cancer in either primary or metastatic sites. The primary cancer also possessed a component of tubular adenocarcinoma which was associated with only a few eosinophils. Hence, we speculate that an eosinophil mobilizing (chemotactic and/or proliferating) factor (s) was produced by the signet ring cancer cells.     

Molecular analysis of Cryptococcus neoformans mitochondrial cytochrome b gene sequences

Mitochondrial cytochrome b genes (cyt b) of 40 strains of Cryptococcus neoformans were partially sequenced to determine the genetic relations. With the exception of the type strain of C. neoformans var. neoformans, all strains contained introns in their sequences. Analysis of 386 bp of coding sequence from each strain under investigation revealed a total of 27 (6.99%) variable nucleotide sites and categorized isolates of C. neoformans into nine cyt b types. C. neoformans var. gattii included cyt b types I to V, and C. neoformans var. neoformans comprised types VI to IX. cyt b types were correlated with serotypes. All strains with cyt b types I, IV, and V were serotype B. All other strains except IFM 5878 (serotype B) with cyt b types II and III were serotype C. Serotype D strains had cyt b types VI and IX, and serotype A strains were cyt b type VIII. Of four serotype AD strains, one was cyt b type VII and the remaining three were type VIII. The phylogenetic tree based on deduced amino acid sequences divided the strains only into C. neoformans var. neoformans and C. neoformans var. gattii. These results indicate that cyt b sequences are effective for DNA typing as well as phylogenetic analysis of C. neoformans.     

Prognostic significance of histologic grade and nuclear expression of beta-catenin in synovial sarcoma

Synovial sarcoma, which has a wide spectrum of biologic behavior, warrants accurate grading to assess the patient's prognosis. We studied the clinicopathologic and immunohistochemical features of 44 cases of synovial sarcoma in patients treated primarily or secondarily at the National Cancer Center, Tokyo, to identify independent prognostic factors. There were local recurrences in 16 patients (36%), and 25 (57%) developed metastases, primarily to the lungs. The estimated cumulative 5-year and 10-year survival rates were 68% and 41%, respectively. Variables associated with an adverse outcome included tumor size > 6.7 cm; initial treatment outside the National Cancer Center; poorly differentiated subtype; high nuclear atypia; mitosis count > 27/10 high-power fields; tumor necrosis; absence of stromal calcification; nuclear expression of beta-catenin, which was found in 25 cases (57%); Ki-67 (MIB-1) index > 27%; and histologic grade 3. Nuclear accumulation of beta-catenin as a cell-signaling event may play an important role in the progression of synovial sarcoma and therefore might be predictive of short survival. However, multivariate analysis clearly showed that only histologic grade, as defined by using categorized variables for the MIB-1 index and tumor necrosis, was an independent prognostic factor. Most variables were correlated with lung metastasis and histologic grade. High-grade synovial sarcoma assessed by a histologic grading system based on the proliferative activity of the neoplastic cells can be viewed as high risk with the patients most likely to die of disease within 10 years after surgery and in need of improved chemotherapy. HUM PATHOL 32:257-263.     

Protective effect of recombinant neutrophil elastase inhibitor (R-020) on sepsis-induced organ injury in rat

Severe inflammatory responses after major surgeries, trauma, and infection develop multiple organ dysfunction. In the mechanisms of the pathogenesis of these responses, activated neutrophils are thought to be important in terms of their ability to produce various kinds of proteinases, which can degrade various proteins constructing human tissues. Among their proteinases, neutrophil elastase is the strongest serine proteinase secreted from activated neutrophils. Thus, we examined in this study the inhibitory effect and therapeutic efficacy of newly produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded the second domain of human urinary trypsin inhibitor. R-020 was effective in significantly improving the survival rate after induction of the rat lethal peritonitis model (cecal ligation and punctureinduced septic shock model). We suggest that various serine proteinases are implicated in the pathogenesis of neutrophil-related multiple organ failure and that recombinant human Kunitz-type proteinase inhibitor might be effective in the treatment of these kinds of organ dysfunction.     

Comparative chromosome mapping of sex-linked genes and identification of sex chromosomal rearrangements in the Japanese wrinkled frog (Rana rugosa, Ranidae) with ZW and XY sex chromosome systems

There are regional variations of sex chromosome morphologies in the Japanese wrinkled frog, Rana rugosa (2n = 26): heterogametic ZZ/ZW-type and XX/XY-type sex chromosomes, and two different types of homomorphic sex chromosomes. To search for homology between the ZW and XY sex chromosomes and the chromosome rearrangements that have occurred during sex chromosomal differentiation in R. rugosa, we performed chromosome mapping of sexual differentiation genes for R. rugosa by FISH. Three genes, AR, SF-1/Ad4BP and Sox3, were localized to both the ZW and XY chromosomes, and their locations were all different between the Z and W and between the X and Y. AR and SF-1/Ad4BP were located on the short arms of the W and X and the long arms of Z and Y, and Sox3 was mapped to the different locations on the long arms between the Z and W and between the X and Y, probably as a result of multiple rearrangements that occurred during the process of sex chromosome differentiation. However, the chromosomal locations of three genes were almost consistent between the Z and Y and between the W and X, indicating that the Z and Y chromosomes and the W and X chromosomes were respectively derived from the same origins. Dmrt1, which is located on avian sex chromosomes, was localized to autosomes in R. rugosa with both the ZW and XY sex chromosomes, suggesting that Dmrt1 might not be related to sex determination in this species.     

Improved enzyme-linked immunosorbent assay using C-terminal truncated recombinant antigens of Babesia bovis rhoptry-associated protein-1 for detection of specific antibodies

An enzyme-linked immunosorbent assay (ELISA) based on a recombinant rhoptry-associated protein-1 (RAP-1) of Babesia bovis has been previously developed, but it was imperfect because some cross-reactions were still present in Babesia bigemina-infected bovine sera. To improve its accuracy for the specific detection of the antibodies to B. bovis, we constructed three C-terminal truncated recombinant antigens of the RAP-1-rCT1 (amino acids [aa] 301 to 408), rCT2 (aa 388 to 490), and rCT3 (aa 466 to 565)-by using a baculovirus expression system and evaluated their diagnostic potentials using ELISA. rCT1 and rCT2 were better diagnostic antigens in their sensitivities and diagnostic efficiencies than rCT3, although none of the recombinant antigens showed any cross-reactivity to B. bigemina-infected bovine sera. These results confirmed that the N-terminal 300-aa region caused cross-reactivity of the entire RAP-1 antigen, and the C-terminal truncated recombinant antigens were shown to be useful reagents for species-specific serodiagnosis.     

IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response

IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR.