Serum H‐ficolin levels: Clinical association with interstitial lung disease in patients with systemic sclerosis

Ficolins, a group of oligomeric lectins consisting of three isoforms (H‐, L‐ and M‐ficolin), contribute to innate immunity via activating the complement pathway and/or acting directly as opsonins against pathogens and apoptotic cells. Because apoptotic cells likely drive the development of systemic sclerosis (SSc) partly through innate immunity, we assessed the clinical association of serum H‐ficolin levels in SSc patients. Despite no difference in serum H‐ficolin levels between SSc and control subjects, SSc patients with decreased serum H‐ficolin levels tended to have a higher prevalence of interstitial lung disease (ILD). More importantly, serum H‐ficolin levels inversely correlated with ground‐glass opacity score on chest computed tomography in SSc‐ILD patients. Therefore, H‐ficolin‐related innate immunity may be involved in SSc‐ILD development.     

Bisphosphonate-related osteonecrosis of the jaw around dental implants in the maxilla: report of a case

Objective: We describe a patient who developed bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) around implants in the upper molar area.
Patients and methods: The patient was a 54-year-old woman with ulceration of the gum, bone exposure, and severe spontaneous pain around implants in the upper left molar area. She had received BPs intravenously for 2 years to treat bone metastases of breast cancer. She was diagnosed with BP-related ONJ. Sequestrum including implants was resected, and hyperbaric oxygen therapy was performed. Undecalcified ground sections were prepared from the resected bone around the implants and stained with toluidine blue. For the bone around the lesion, decalcified sections were prepared, and examined by histological and immunohistological analysis.
Results: The surgical wound became completely covered with mucosal epithelia, and postoperative pain disappeared. No recurrence of ONJ was noted during a 6-month postoperative follow-up period. However, the patient died from metastatic disease. Although histopathological examination of the resected jaw bone revealed sequestrum, osseointegration of the implant was maintained. In the area around the lesion, there was no progression of bone necrosis, and reactive bone formation, fibrosis, and invasion of lymphoid cells into the marrow cavity were observed.
Conclusion: There is no effective treatment for ONJ caused by BPs, and conservative therapy based on clinicians' experience is recommended. However, if chemotherapy is planned, or if bone necrosis around implants is thought to harbor infection, the option of jaw resection should be considered.     

Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative.

PURPOSE: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. EXPERIMENTAL DESIGN: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. RESULTS: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. CONCLUSIONS: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.     

Prevention by acetylsailcylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino acid-defined diet in rats

Effects of acetylsailcylic acid (ASA) (aspirin) on the pathogenesisof fatty liver, cirrhosis and hepatocarcinogenesis caused bya choline-deficient L-amino acid-defined (CDAA) diet were examinedin male Fischer 344 rats fed a CDAA diet supplemented with 0,0.1, 0.2, 0.4 or 0.8% ASA for 30 weeks. ASA at concentrationsof >0.2% prevented the development of both cirrhosis andpreneoplastic and neoplastic nodules, but without any directlyassociated prevention of fatty changes. ASA also prevented hepatocyteproliferation and the generation of thiobarbituric acid-reactivesubstances and 8-hydroxydeoxyguanosine caused by feeding theCDAA diet, analyzed, respectively, after 1, 12 and 12 weeks.The results clearly indicate that the anti-inflammatory drugASA, which is not a lipotropic factor, can prevent the pathogenesisof cirrhosis and hepatocarcinogenesis caused by a CDAA diet,which is possibly partly associated with the prevention of reactiveoxygen species production.     

Different Roles of 8-Hydroxyguanine Formation and 2-Thiobarbituric Acid-reacting Substance Generation in the Early Phase of Liver Carcinogenesis Induced by a Choline-deficient, l-Amino Acid-defined Diet in Rats

The present study was performed to assess the roles of hepatocellular oxidative damage to DNA and constituents other than DNA in rat liver carcinogenesis caused by a choline-deficient, l -amino acid-defined (CDAA) diet by examining the effects of the antioxidant N, N' -diphenyl- p -phenylenediamine (DPPD). The parameters used for cellular oxidative damage were the level of 8-hydroxyguanine (8-OHGua) for DNA and that of 2-thiobarbituric acid-reacting substance (TBARS) for constituents other than DNA. A total of 40 male Fischer 344 rats, 6 weeks old, were fed the CDAA diet for 12 weeks with or without DPPD (0.05, 0.10 or 0.20%) or butylated hydroxytoluene (BHT, 0.25%). In the livers of the rats, the numbers and sizes of glutathione S -transferasc (EC 2.5.1.18) placental form (GSTP)- and/or γ-glutamyltransferase (GGT, EC 2.3.2.2)-positive lesions and levels of 8-OHGua and TBARS were determined. The GSTP-positive lesions of 0.08 mm² or larger were all stained positively for GGT as well in cross-sectional area, whereas the smaller lesions were generally negative for GGT. DPPD and BHT reduced the size of the GSTP-positive lesions without affecting their total numbers. At the same time, they reduced TBARS generation without affecting 8-OHGua formation in DNA. The present results indicate that oxidative DNA damage (represented by 8-OHGua formation) and damage to constituents other than DNA (represented by TBARS generation) may play different roles in rat liver carcinogenesis caused by the CDAA diet; the former appears to be involved in the induction of phenotypically altered hepatocyte populations while the latter may be related to the growth of such populations.     

Initiation of hepatocarcinogenesis by endogenously formed N-nitrosobis(2-hydroxypropyl)amine, N-nitrosodiethanolamine and N-nitroso-2,6-dimethylmorpholine in rats

Initiation activities of endogenously formed N-nitrosobis(2-hydroxypropyl)amine(NBHPA), N-nitrosodiethanolamine (NDELA) and N-nitroso-2,6-dimethylmorpholine(NDMM) were investigated in a modified short-term assay forrat hepatocarcinogenesis. Male Wistar rats were fed 1 % bis(2-hydroxypropyl)amine,0.5% diethanolamine or 0.25% 2,6-dimethylmorpholine in the dietplus 0.3% sodium nitrite in the drinking water. Two weeks afterstarting the experimental regimen they underwent 2/3 partialhepatectomy and were then maintained on the respective dietsfor a further week. Following a 2 week recovery period on basaldiet the rats were subjected to a resistant hepatocyte regimenconsisting of 0.02% 2-acetylaminofluorene in the diet for 2weeks and 1 mg carbon tetrachloride/kg body wt by gavage atthe midpoint. Initiation activity was assayed by measuring hepaticfoci positive for     

Prevention by Methionine of Enhancement of Hepatocarcinogenesis by Coadministration of a Choline-deficient L-Amino Acid-defined Diet and Ethionine in Rats

The effects of methionine on hepatocarcinogenesis induced by Coadministration of a choline-deflcient L-amino acid-defined (CDAA) diet and ethionine were examined. F344 male rats were divided into 4 experimental groups. Groups 1 and 2 received the CDAA diet and a choline-supplemented L-amino acid-defined (CSAA) diet, respectively. Group 3 received the CDAA diet containing 0.05% ethionine, and group 4 the CDAA diet containing 0.05% ethionine and 0.47% methionine. Animals were killed after 12 weeks of treatment. Histologically, the CDAA diet induced intracellular fat accumulation and foci. In contrast, ethionine caused not only foci, but also hyperplastic nodules, cholangiofibrosis and the proliferation of oval cells without such fat accumulation. Methionine abolished the development of all of the liver lesions induced by Coadministration of the CDAA diet and ethionine. To investigate the effects of methionine on induction of c- myc and c-Ha- ras expression, as well as generation of 8-hydroxyguanine (8-OHGua) and 2-thiobarbituric acid-reacting substances (TBARS), by Coadministration of the CDAA diet and ethionine, subgroups of 3 to 5 animals were killed at 2, 4, 8 or 11 days after the beginning of the experiment. Coadministration of the CDAA diet and ethionine markedly enhanced the level of expression of c- myc and c-Ha- ras , 8-OHGua formation and TBARS generation as compared with the CDAA or CSAA diet within 11 days, and methionine blocked these actions. These results indicate that addition of methionine prevents the induction of c- myc and c-Ha- ras expression, 8-OHGua formation and TBARS generation, as well as hepatocellular lesions, by Coadministration of the CDAA diet and ethionine in rats, and suggest a possible involvement of oxidative stress and gene expression in hepatocarcinogenesis by these agents.     

Three imported cases of acute Q fever after an inspection tour to Australia and New Zealand

After an inspection tour to farms and abattoirs in Australia and New Zealand, three Japanese persons simultaneously developed febrile illnesses in Japan. They generally had slight fever and general fatigue, followed by thrombocytopenia and hepatic dysfunction. However, no respiratory symptoms were observed. In one of the cases, severe thrombocytopenia (1.3 x 10(4)/microliter) and high fever up to 40 degrees C were observed. These clinical symptoms were compatible with Q fever. All of the cases showed four hold-elevations of IgM and IgG against Coxiella burnetii phase II between acute and convalescent sera by a serological test. C. burentii-DNA was also detected in the serum of one patient. Minocycline was highly effective in all cases. This report illustrates the typical clinical courses of acute Q fever.