Epstein-Barr Virus-positive Intestinal Diffuse Large B-cell Lymphoma in a Japanese Patient with Celiac Disease: First Reported Case and a Literature Review

A 60-year-old Japanese woman was diagnosed with celiac disease (CeD) and treated with a gluten-free diet. For five years, she had a good clinical course. However, she complained of inappetence and nausea. Colonoscopy revealed ulcerative tumors in the terminal ileum. A histological examination of biopsy specimens from the ulcerative tumor showed diffuse infiltration of large atypical lymphocytes. Immunohistologically, the atypical lymphoid cells were positive for cluster of differentiation (CD)10 and CD20. Many Epstein-Barr virus-encoded small RNA (EBER)-positive atypical lymphocytes were detected by in situ hybridization. This represents the first reported case of Epstein-Barr virus-positive intestinal diffuse large B-cell lymphoma complicated with CeD.     

Intracranial trajectories of sympathetic nerve fibers originating in the superior cervical ganglion in the rat: WGA-HRP anterograde labeling study

Intracranial trajectories of sympathetic nerve fibers originating in the superior cervical ganglion (SCG) in the rat were investigated by means of anterograde labeling following the injection of wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) into the unilateral SCG. The trajectory of the sympathetic fiber innervating the pineal gland and its continuing structures was found advancing along the abducent nerve, through the cavernous plexus, then along the trochlear nerve. Labeled sympathetic fibers showed two patterns of distribution in the blood vessels on the basal surface of the brain. The sympathetic fibers originating in the unilateral SCG were intermingled with those fibers from the contralateral SCG in the pineal gland, its continuing structures and the choroid plexus of the third ventricle as well as in the cerebral blood vessels.     

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a valuable diagnostic marker for rupture of thin-cap fibroatheroma: Verification by optical coherence tomography

Background

Relationships between plaque morphology on optical coherence tomography (OCT) and biomarker levels in the patients with acute coronary syndrome (ACS) have not been fully investigated.

Methods

ACS patients (n = 128) were prospectively enrolled and their plasma levels of soluble lectin-like oxidized LDL receptor-1 (sLOX-1), high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity troponin T (hs-TnT) were measured. Another set of 20 patients with stable angina pectoris (SAP) without plaque rupture or erosion served as controls. Among 128 ACS patients, 75 patients underwent OCT procedure to evaluate culprit plaque morphology, and were categorized into two groups; ACS with plaque rupture (ruptured ACS; R-ACS, n = 54) and ACS without plaque rupture (non-ruptured ACS; N-ACS, n = 21).

Results

Levels of sLOX-1 (p < 0.001), hs-CRP (p = 0.048) and hs-TnT (p < 0.001) were significantly higher in R-ACS than SAP. Levels of sLOX-1 were also significantly higher in R-ACS than in N-ACS (p < 0.001); whereas levels of hs-CRP (p = 0.675), as well as those of hs-TnT (p = 0.055), were comparable between R-ACS and N-ACS. Comparison of receiver operating characteristic (ROC) curves among sLOX-1, hs-CRP and hs-TnT to differentiate R-ACS from N-ACS revealed that the area under the curve (AUC) values of sLOX-1, hs-CRP and hs-TnT were 0.782, 0.531 and 0.643, respectively. ROC curves, generated for these biomarkers, to differentiate ACS with thin-cap fibroatheroma (TCFA) from those without demonstrated that the AUC values of sLOX-1, hs-CRP and hs-TnT were 0.718, 0.506 and 0.524, respectively.

Conclusion

sLOX-1, but not hs-CRP or hs-TnT, can differentiate ACS with plaque rupture from those without, and ACS with TCFA from those without.     

Difference in Left Ventricular Mass Index Between Hypertensive Patients With and Without Renal Artery Stenosis by Propensity Score Analysis

This study aimed to define the difference in cardiac hypertrophy between hypertensive patients with and without renal artery stenosis (RAS). When cardiac ultrasonographic examination was performed in 971 consecutive hypertensive outpatients, renal peak systolic velocity (PSV) was examined. Compared with patients without RAS, those with RAS (PSV ≥180 cm/s, 4.1%) were significantly older and included a higher proportion of male patients and had a higher left ventricular mass index (LVMI). A stratified analysis in the selected 120 patients showed that the LVMI was significantly higher in patients with RAS than in those without RAS for each confounding factor such as age and blood pressure. RAS was independently associated with a higher LVMI on propensity score analysis and multivariate analysis. Thus, the difference in LVMI between hypertensive patients with and without RAS was confirmed, irrespective of age and blood pressure, by stratified propensity score analysis and multivariate regression analysis.     

Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects

Objective: Gastric cancer (GC) and adenoma (GA) are reported to be related to atrophic gastritis, in which the serum pepsinogen (PG) I level and the PGI/PGII ratio (I/II ratio) are reduced. To verify that the finding of a low PG level increases the risk for GC and GA, we investigated the correlation between low PG levels and the prevalence of GC and GA in individuals.
Methods: The 2,039 subjects (734 Japanese men, mean age 68.5 yr, and 1,305 women, mean age 66.7 yr), selected from among 10,996 local residents who underwent health check-ups based on reductions in their serum PG levels, underwent upper gastrointestinal endoscopy.
Results: Gastrointestinal endoscopy detected 21 GCs and 15 GAs. The prevalence of GC was higher than that in the residents without low serum PG. The percentage of early stage of GC (90%) was significantly higher than that of GC detected in unscreened residents (56.9%). The prevalence of GC in men was closely and significantly correlated with the I/II ratio (  r = 0.935  ,   p = 0.0063  ), whereas there was less correlation with age (  r = 0.842  ,   p = 0.0734  ). The prevalence of GA was also closely and significantly correlated with the I/II ratio in men (  r = 0.881  ,   p = 0.0203  ), but not with age (  r = 0.163  ,   p = 0.7928  ). In women the prevalence of GC (r 5 0.744,   p = 0.090  ) and GA (  r = 0.678  ,   p = 0.1392  ) did not correlate as strongly with the I/II ratio, although the highest prevalence was seen in the group with the lowest I/II ratio.
Conclusion: Our study verified that a low I/II ratio signifies a high risk for GC and GA and that measuring serum PG levels can be used as a screening method for GC and GA.     

Phase I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study

The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of gemtuzumab ozogamicin (GO) in patients with relapsed and/or refractory CD33-positive acute myeloid leukemia (AML). Patients received 2-h infusions of GO twice with an interval of approximately 14 days. Tolerability was assessed using the National Cancer Institute Common Toxicity Criteria Version 2.0. Samples for pharmacokinetics were taken on day 1 and day 8 of the first treatment cycle. The dose was increased stepwise and, in each cohort, patients were treated at the same dose. Forty patients, median age 58 years (range 28–68) were treated; 20 and 20 patients were enrolled to the phase I and II parts, respectively. In the phase I part, dose-limiting toxicities (DLTs) were hepatotoxicities, and the recommended dose was established as 9 mg/m² given as two intravenous infusions separated by approximately 14 days. The pharmacokinetic study revealed that C _max and AUC were equivalent to those of non-Japanese patients. In the phase II part, complete remission was observed in 5 patients, and one patient had complete remission without platelet recovery. Four of these 6 in remission and one in the phase I are long-term survivors (alive for at least 44 months). GO is safe and effective as a single agent among Japanese CD33-positive AML patients. Remission lasted longer in a subset of patients than in non-Japanese patients in earlier studies. Further studies of this agent are warranted to establish standard therapy. S. Furusawa: deceased.     

Helicobacter pylori stimulates inducible nitric oxide synthase in diverse topographical patterns in various gastroduodenal disorders

Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) acts cytotoxically and contributes to inflammation. We explored the roles of iNOS in the pathogenesis of Helicobacter pylori-associated diseases. Using reverse-transcribed PCR, we examined topographical patterns of iNOS mRNA expression in the gastroduodenal mucosa in H. pylori-negative controls and H. pylori-positive patients with duodenal ulcer (DU), gastric ulcer (GU), and ulcer-free gastritis. iNOS expression showed topographical variations among the tested disorders. As compared to controls, DU had a significantly higher expression of iNOS mRNA in the duodenum, GU in the antrum and duodenum, and gastritis in the antrum and corpus. H. pylori eradication yielded a significant reduction of iNOS mRNA in the duodenum of DU and in the antrum of GU. Diverse topographical patterns of H. pylori-induced iNOS expression may contribute to mechanisms by which H. pylori elicits different clinical disorders.