An anti-nuclear antibody-negative patient with systemic lupus erythematosus (SLE) accompanied with anti-ribosomal P antibody (anti-P)

We report a case of an anti-nuclear antibody (ANA)-negative patient with systemic lupus erythematosus (SLE) accompanied with anti-phospholipid antibody syndrome (APS) and lupus nephritis (LN). Histological examination of placenta obtained by an artificially-induced abortion revealed multiple thromboses in the placental villi. Histology of biopsied kidney tissue revealed minimal change with deposits of immunoglobulin and complement. Anti-ribosomal P antibodies (anti-P) and lupus anticoagulant (LAC) were positive and anti-double stranded DNA antibody (anti-DNA) showed only a slightly positive titer in her serum. The intensity of proteinuria of the patient was correlated with the anti-P, but not anti-DNA titers.     

Metastasis of uterine leiomyosarcoma to the pancreas--usefulness and limitations of EUS-FNA

A woman in her 60's presented with a tumor of the pancreatic body. Pan-hysterectomy had been performed under a diagnosis of uterine leiomyoma 11 years previously. A sample obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed the histopathological proliferation of spindle-shaped bundles of atypical cells, and immunohistochemical staining demonstrated that these cells were positive for KIT. Therefore, distal pancreatectomy was performed under a diagnosis of pancreatic gastrointestinal stromal tumor (GIST). Immunohistochemical staining of surgical specimens demonstrated that the tumor cells were positive for desmin and negative for KIT and CD34. The low-grade leiomyosarcoma in pathological specimens of the uterine myoma obtained 11 years previously histologically resembled the pathological findings of the pancreatic specimens except for atypical nuclei and mitotic cells. Therefore, the final diagnosis was extremely rare metastatic leiomyosarcoma of the pancreas. Herein, we report metastasis of uterine leiomyosarcoma to the pancreas and discuss the usefulness and limitations of EUS-FNA.     

Successful Therapy Using Pasireotide Long-acting Release for Cushing's Disease Merged with Biochemical Acromegaly

It is quite rare that Cushing''s disease shows acromegaly, and no pharmacotherapy has yet been discussed. A 21-year-old woman was diagnosed with Cushing''s disease and underwent trans-sphenoidal surgery. Five years later, she was diagnosed with recurrent Cushing''s disease and biochemical acromegaly because of elevated levels of serum growth hormone (GH), plasma insulin-like growth factor-1, plasma adrenocorticotropic hormone (ACTH), and the 24-hour urinary excretion of free cortisol. After treatment initiation with pasireotide-long-acting release (LAR), both the ACTH and GH declined. Our case is the first to show the efficacy of pasireotide-LAR in controlling both Cushing''s disease and acromegaly.     

Power Doppler and spectral Doppler measurements of knee-joint synovitis in rheumatoid arthritis patients with superficial pattern signals and in those with deep pattern signals

Power Doppler and spectral Doppler ultrasonography were used to scan 127 knee joints of 72 patients with rheumatoid arthritis (RA). Synovial effusion thickness and synovial proliferation (pannus) thickness, as well as the flow signal diameter, were measured on ultrasonogram prints of the power Doppler using digital calipers. In addition, color-flow signal grades on power Doppler and the resistance index (RI) values on spectral Doppler were evaluated. The values of these five variables were compared among 58 joints with superficial pattern flow signals and 69 joints with deep pattern flow signals. Compared with the joints with deep pattern signals, the joints with superficial pattern signals had significantly higher mean values of effusion thickness (P < 0.0001) and flow signal grades (P < 0.0001), and significantly lower mean RI (P < 0.0001). On the other hand, the joints with deep pattern signals had a significantly higher value of signal diameter (P = 0.0125) and had a trend to higher value of pannus thickness (P = 0.079) as well. Significant correlations were observed between effusion thickness and signal grades (P < 0.0001); effusion thickness and RI (P < 0.0001); signal diameter and pannus thickness (P = 0.0102); signal diameter and RI (P < 0.0001); and signal grades and RI (P < 0.0001). The ultrasonographic measurements of synovitis in RA patients provide valuable information on synovial inflammation.     

Doppler sonographic comparative study on usefulness of synovial vascularity between knee and metacarpophalangeal joints for evaluation of articular inflammation in patients with rheumatoid arthritis treated by infliximab

We used Doppler sonography to evaluate the therapeutic effects of infliximab on the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid arthritis (RA), based on the color flow signals (CFS) and resistance index (RI) of synovial vascularity. After three injections of infliximab, we observed significant improvement in numbers of tender joints (P < 0.01), values of C-reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P < 0.001), disease activity scores including tender joints, swollen joints, and ESR (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints. There was no significant improvement in RI values of knee or MCP joints after the therapy. We observed significant correlation between CFS of knee joints (knee-CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3. However, no significant correlation was observed between 10 difference values (before values–after values) of CFS grades of knee or MCP joints and 10 difference values each of CRP, ESR, or DAS28-E3. The knee joints are more suitable than MCP joints for obtaining CFS in Doppler sonography, and are more useful than MCP joints for evaluation.     

Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C

BACKGROUND/AIMS: Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation-related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy. METHODS: Hepatic accumulation of 8-nitroguanine and 8-OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non-alcoholic fatty liver. RESULTS: Immunoreactivities of 8-nitroguanine and 8-OHdG were strongly detected in the liver from patients with CHC, but not in control livers. 8-Nitroguanine accumulation was found not only in infiltrating inflammatory cells, but also hepatocytes particularly in the periportal area. The accumulation of 8-nitroguanine and 8-OHdG increased with inflammatory grade (8-nitroguanine; P = 0.0019, 8-OHdG; P = 0.0009). In the sustained virological responder group after interferon therapy, 8-nitroguanine and 8-OHdG accumulation were markedly decreased in the liver (8-nitroguanine; P = 0.018, 8-OHdG; P = 0.018). CONCLUSIONS: In this study, we demonstrated for the first time that 8-nitroguanine accumulated in the liver of patients with CHC. 8-Nitroguanine is a useful biomarker to evaluate the severity of HCV-induced chronic inflammation in relation to hepatocellular carcinoma.     

Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes

We provide here evidence that supports the occurrence of a biologically dormant form of selectin ligand carbohydrate, the sialyl 6-sulfo Lewis X containing modified sialic acid, in human leukocytes. The modification of sialic acid involves first de-N-acetylation of sialic acid moiety through ubiquitous de-N-acetylation/re-N-acetylation cycle, followed by the dehydrative cyclization of de-N-acetyl sialic acid to form “cyclic sialic acid.” The enzyme involved in the dehydration of de-N-acetyl sialic acid is a calcium-dependent enzyme having neutral–alkaline pH optimum. De-N-acetyl sialyl 6-sulfo Lewis X retained selectin binding activity as well as parental sialyl 6-sulfo Lewis X, but cyclic sialyl 6-sulfo Lewis X was devoid of selectin binding activity. Sialyl 6-sulfo Lewis X carrying the cyclic sialic acid is specifically recognized by the newly generated mAb, G159. The determinant was distributed widely among normal human leukocytes, especially on monocytes and subsets of lymphocytes including NK cells, helper memory T cells, Tcr-γδ T cells, and a part of B cells. The determinant was detected also on several cultured lymphocytic leukemia cell lines and O-tetradecanoylphorbol 13-acetate-activated lymphoid cells. Cyclic sialyl 6-sulfo Lewis X is efficiently formed by the action of the partly membrane-bound calcium-dependent enzyme, tentatively called “sialic acid cyclase,” and a possible physiological significance of this reaction could be a rapid inactivation of selectin binding activity at the cell surface. Conversely, the accumulated intracellular cyclic sialyl 6-sulfo Lewis X determinant may function as a dormant pool of selectin ligands, which, on appropriate stimulation, is hydrolyzed and becomes active in selectin-dependent cell adhesion.     

Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography (FDG-PET/CT)

Background

The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT).

Methods

Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard.

Results

In all, 270 colorectal lesions 5?mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11?mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21?mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10?mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44?C221.67] and flat morphology (OR 7.78, 95% CI 1.79?C36.25) were significant factors that were associated with false-negative cases on PET/CT.

Conclusion

The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results.     

Platelet-derived adenosine 5'-triphosphate suppresses activation of human hepatic stellate cell: In vitro study

Aim: Activated hepatic stellate cells (HSC) play a critical role in liver fibrosis. Suppressing abnormal function of HSC or reversion from activated to quiescent form is a hopeful treatment for liver cirrhosis. The interaction between platelets and HSC remains unknown although platelets go through hepatic sinusoids surrounded by HSC. This study aimed at clarifying the hypothesis that platelets control activation of HSC. Methods: We used human platelets, platelet extracts, and primary or immortalized human HSC. We examined the effect of platelets on the activation, DNA synthesis, type I collagen production, and fibrosis-relating gene expressions of HSC. We investigated what suppressed activation of HSC within platelets and examined the mechanism of controlling activation in vitro. Results: Platelets and platelet extracts suppressed activation of HSC. Platelets decreased type I collagen production without affecting DNA synthesis. Platelets increased the expression of matrix metallopeptidase 1. As platelet extracts co-cultured with an enzyme of degrading adenosine 5'-triphosphate (ATP) suppressed activation, we detected adenine nucleotides within platelets or on their surfaces and confirmed the degradation of adenine nucleotides by HSC and the production of adenosine. Adenosine and platelets increased the intracellular cyclic adenosine 5'-monophosphate (cAMP), which is important in quiescent HSC. A great amount of adenosine and ATP also suppressed activation of HSC. Conclusion: Activation of human HSC is suppressed by human platelets or platelet-derived ATP via adenosine-cAMP signaling pathway in vitro. Therefore, platelets have the possibility to be used in the treatment of liver cirrhosis.