EB virus-associated peripheral T cell lymphoma presenting with hemophagocytic syndrome and hepatic cell necrosis

A 72-year-old woman was admitted with left cervical lymphadenopathy, high fever, pancytopenia and liver dysfunction. Bone marrow aspiration showed infiltration of large atypical lymphoid cells and hemophagocytic histiocytes, thus suggesting a diagnosis of lymphoma associated hemophagocytic syndrome (LAHS). An abdominal CT scan revealed multiple low-density areas in the liver, and the patient's liver function rapidly deteriorated. Histologically, the cervical biopsy showed lymphoma cell infiltration with prominent necrosis and karyorrhectic debris. The lymphoma cells expressed CD3+, CD4-, CD8+, CD20-, CD56+/-, TIA-1+, granzyme B+, and EBER was positive using in situ hybridization. DNA analysis of the TCR beta and gamma chain gene with the Southern blot showed rearranged bands. These findings were compatible with those of EB-virus associated peripheral T-cell lymphoma. After chemotherapy with the THP-COP regimen, the patient's liver dysfunction improved rapidly, but she died from bacterial peritonitis due to perforation of a recurrent duodenal ulcer. Post-mortem examination of the liver showed multiple irregular massive necroses of the hepatocytes, where no lymphoma cell infiltration was present. Hemophagocytic histiocytosis was remarkable in the bone marrow, spleen, lymph nodes, and liver. Marked elevation of serum levels of cytokines such as TNF-alpha or IFN-gamma suggests that these cytokines played an important role in the pathogenesis of the hepatic cell necrosis.     

Alteration in the retinoblastoma gene associated with immortalization of human fibroblasts treated with60Co gamma rays

Genetic analysis was carried out in human fibroblasts (KMST-6) immortalized by treatment with⁶⁰Co gamma rays in order to determine if any genetic change was involved in the immortal transformation of human cells. Analysis by restriction fragment length polymorphism revealed an alteration in chromosome 13q12–14, in which the retinoblastoma (RB) gene locus (13q14) is located. Then the RB gene itself was examined. Structural abnormalities in the RB gene were detected by Southern blot analysis. Furthermore, abnormal RB protein (pRB) was expressed in immortalized KMST-6 cells, as shown by in vitro phosphorylation, whereas normal KMS-6 cells expressed the intact pRB. These findings indicated that inactivation of the RB gene is one of the key events of the immortalization of human cells.Abbreviations RB retinoblastoma - pRB retinoblastoma gene product (protein) - T simian virus 40 large T antigen - E1A adenovirus E1A protein     

Influence of bone parameters on peri-implant bone strain distribution in the posterior mandible

Objectives: The success rate of dental implants depends on the type of bone at the implant site. The purpose of the present study was to investigate the effects of the bone parameters at the implant-placement site on peri-implant bone strain distributions. Study Design: The morphologies and bone densities of seventy-five potential implant sites in the posterior mandible were measured using computed tomography (CT). Based on the CT data, we defined bone parameters (low and high in terms of cancellous-bone density and crestal-cortical bone density, and thin and thick in terms of crestal-cortical bone thickness), and we constructed finite-element models simulating the various bone types. A buccolingual oblique load of 200 N was applied to the top of the abutment. The von Mises equivalent (EQV) strains in the crestal-cortical bone and in the cancellous bone around the implant were calculated. Results: Cancellous-bone density greatly affected the maximum EQV strain regardless of the density and thickness of the crestal cortical-bone. The maximum EQV strains in the crestal cortical-bone and the cancellous bone in the low-density cancellous-bone models (of 150 Hounsfield units (HU) were 1.56 to 2.62-fold and 3.49 to 5.31-fold higher than those in the high-density cancellous-bone models (of 850 HU), respectively. The crestal cortical-bone density affected the maximum EQV strains in the crestal cortical-bone and in the cancellous bone in the low-density cancellous-bone models. The crestal cortical-bone thickness affected the maximum EQV strains in the cancellous bone and in the crestal cortical-bone in the low-density cancellous-bone models. Conclusions: Our results confirm the importance of bone types for the peri-implant bone strain distribution. Cancellous-bone density may be a critical factor for peri-implant bone strain. Key words:Dental implant, bone density, finite-element analysis.     

Duodenal gastric heterotopia,sporadic or fundic gland polyp-associated,frequently carries β-catenin mutation

Duodenal gastric heterotopia (DGH) is a benign asymptomatic condition assumed to be of congenital origin. Since DGH is often associated with fundic gland polyps (FGPs) that frequently carry a somatic β-catenin gene mutation, we examined whether DGH, either sporadic or FGP-associated, is attributable to alterations of the Wnt/β-catenin pathway. Genetic analysis revealed frequent somatic β-catenin gene mutations in DGH; some of which showed the same mutation pattern as coexisting FGPs. All missense mutations were confined to codons 32, 33, and 37. No such mutations were observed, however, in any of the specimens from focal gastric foveolar metaplasia (GFM). Therefore, DGH is not a mere congenital lesion due to aberrant migration of normal gastric mucosa or a simple reactive metaplasia after regenerative stimuli of the duodenal mucosa, but a distinct condition based upon molecular genetic changes in the Wnt/β-catenin pathway.     

Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis

To elucidate the associations between Lp(a) levels and coronary and aortic atherosclerosis, we performed aortic MRI in 143 patients undergoing coronary angiography. Severity of aortic atherosclerosis was represented as plaque scores. Of the 143 patients, 104 had coronary artery disease (CAD). Thoracic and abdominal aortic plaques were found in 89 and 131 patients. Lp(a) levels increased stepwise with the number of stenotic coronary vessels: 15.7 (CAD(-)), 21.2 (1-vessel), 21.4 (2-vessel), and 22.9 mg/dl (3-vessel) (P<0.05). For aortic atherosclerosis, 143 patients were divided into quartiles by plaque scores. Lp(a) did not differ among quartiles of thoracic plaques: 17.1, 19.0, 23.5, and 21.2 mg/dl (P=NS), whereas Lp(a) increased stepwise with quartiles of abdominal plaques: 17.1, 19.2, 19.1, and 24.0 mg/dl (P<0.05). Lp(a) was an independent factor for CAD and abdominal aortic plaques, but not thoracic plaques. Thus, Lp(a) levels were associated with aortic atherosclerosis, especially in abdominal aorta, as well as coronary atherosclerosis.     

No evidence of association between 8q24 and susceptibility to nonsyndromic cleft lip with or without palate in Japanese population

Objective : Recent genome-wide association studies identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL±P) on 8q24.21, 10q25.3, 13q31.1, 15q13.3, 17q22, and 18q22 in populations of European origin. The purpose of this study was to determine, using DNA samples, whether 8q24.21 was a susceptibility locus for the development of NSCL±P in Japanese patients. Methods : We used DNA from 167 Japanese NSCL±P patients (45 cleft lip without cleft palate and 122 cleft lip with cleft palate patients) and 190 Japanese unaffected control individuals. We performed an association study using 13 single nucleotide polymorphisms (SNPs) selected on the 8q24.21 locus. Genotyping of each SNP was carried out by direct sequencing of genomic DNA. Additionally, a haplotype block was constructed using the selected SNPs. Results : The 13 selected SNPs were successfully genotyped in 357 individuals. The p values obtained were not low enough to indicate a significant association between the haplotypes and the development of NSCL±P in this population. Conclusions : Our results suggest that the 8q24.21 locus is not associated with susceptibility to NSCL±P in Japanese patients and provide further evidence that ethnicity is a strong factor in determining susceptibility loci, albeit using a limited number of samples. Further studies are needed to identify regions involved in the development of NSCL±P in the Japanese population.