Ryuichi Nagashima

Regression of duodenal mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori.

It is rare for low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) to affect the duodenum, and no reports have mentioned any relationship between this disease and Helicobacter pylori infection. This case report describes a patient with multiple small erosions and diffuse erythema in the duodenal bulb diagnosed histopathologically as MALT lymphoma. Immunoglobulin (Ig) heavy-chain gene rearrangement was detected, and monotypic plasma cell proliferation (IgG kappa) was shown by immunohistochemistry. The lesion was localized to the duodenal bulb. Antibiotic therapy for H. pylori resulted in resolution of the morphological features of the lymphoma, as confirmed by endoscopic and pathological examination. Moreover, the gene rearrangement could not be detected after eradication of the bacterium. Although additional follow-up is needed, it is suggested that H. pylori eradication therapy may be effective for patients with MALT lymphoma in the duodenum as well as the stomach.

Helicobacter pylori antigen in the glomeruli of patients with membranous nephropathy.

Abstract Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori.We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN.

13C-Urea breath test, using a new compact nondispersive isotope-selective infrared spectrophotometer: comparison with mass spectrometry.

BackgroundThe 13C-urea breath test (13C-UBT) is the most commonly used noninvasive method of detecting Helicobacter pylori infection. The isotope ratio mass spectrometer (IRMS) is the most commonly used device for this test, but the UBiT-IR300 infrared spectrophotometer, which, by comparison, is a more compact, less expensive, and easier to use analytical device, has now become widely used in the clinical setting in Japan. The objective of this study was to examine the diagnostic performance of the 13C-UBT, using the UBiT-IR300.MethodsA multicenter open-label study was performed, in which the 13C-UBT was conducted using 100 mg of 13C-urea. Analysis of 13CO2 in the expired breath was performed by infrared spectroscopy and mass spectrometry, and assessment of H. pylori infection was performed by culture, histological examination, and rapid urease test.ResultsIn 255 cases of H. pylori infection diagnosed by biopsy methods, the 13C-UBTs, performed with two different 13C-ruea formulations, and using infrared spectroscopy for evaluation, showed a sensitivity of 97.7%, specificity of 98.0%, and accuracy of 97.8% (total number of evaluable cases, n = 505). The rate of agreement in the assessment of H. pylori infection between infrared spectroscopy and mass spectrometry was 100% (n = 505). The regression equation for infrared spectroscopy to mass spectrometry was y = 0.9822x − 0.0809 (n = 2542), with a correlation coefficient of r = 0.99989 (P = 0.0001).ConclusionsDiagnosis of H. pylori infection can be performed using infrared spectroscopy as well as mass spectrometry.

Comparison between a new 13C-urea breath test, using a film-coated tablet, and the conventional 13C-urea breath test for the detection of Helicobacter pylori infection.

BackgroundIn Japan, urea breath-testing includes mouth rinsing with water immediately after the ingestion of 13C-urea solution, to prevent false-positive results that are caused by oral bacteria with urease activity. Our objective was to evaluate the diagnostic performance of a urea breath test using a film-coated 13C-urea tablet and omitting mouth rinsing.MethodsThe study was a multicenter trial comparing the solution- and tablet-based urea breath tests (UBTs). Helicobacter pylori status was determined by histology, culture, and rapid urease testing.ResultsOf the 255 subjects who completed the study, evaluation of the tablet-based UBT was possible in 254, and comparison of the tablet-based UBT and the solution-based UBT was possible in 250 patients. When the assessment achieved by a combination of biopsy-based methods was used as a reference standard, the sensitivity, specificity, and accuracy of the tablet-based method were determined to be 97.7%, 98.4%, and 98.0%, respectively. When the results of the solution-based UBT were used as a reference standard, the sensitivity, specificity, and accuracy of the tablet-based UBT were determined to be 96.9%, 97.6%, and 97.2%, respectively.ConclusionsThe 13C-urea tablet-based method proved to be a simple and accurate test for the diagnosis of H. Pylori infection. Mouth rinsing was not required.

Esophageal small cell carcinoma with ectopic production of parathyroid hormone-related protein (PTHrp), secretin, and granulocyte colony-stimulating factor (G-CSF).

A patient with primary small cell carcinoma of the esophagus is reported, in whom we have studied the secretion of a variety of hormones and cytokines. The tumor was an intermediate cell type of small cell carcinoma and had either epithelial and neuroendocrinological characteristics. Furthermore, hypercalcemia and neutrophilia were present, and the tumor was shown to produce PTHrp, secretin, and G-CSF. The present case is the first report of primary small cell carcinoma of the esophagus with ectopic production of PTHrp, secretin, and G-CSF.

Case Report: Fecal Clearance of α1-Antitrypsin with Lansoprazole Can Detect Protein-Losing Gastropathy

Detecting plasma protein loss from the stomach is quite difficult by measuring fecal alpha1-AT clearance because alpha1-AT is rapidly destroyed in the gastric juice at values below pH 3. We examined protein loss from the stomach using fecal alpha1-AT clearance with lansoprazole, a proton pump inhibitor. A 38-year-old Japanese male presented with hypoproteinemia (total serum protein: 4.4 g/dl). Abdominal scintigraphy using technetium-99m-labeled albumin revealed distinct radioactivity accumulation in the small intestine. It strongly suggested excessive protein loss to the gastrointestinal tract. Although, regular fecal alpha1-AT clearance was within the normal range (<13 ml/day), the fecal alpha1-AT clearance with the administration of lansoprazole was 80.5 ml/day. The results indicated that this method using lansoprazole is simple and useful for detecting protein-losing gastropathy.

In Vitro Immune Complex Binding Assay to Examine the Mechanism of Immune Complex Trapping by Human Follicular Dendritic Cells (FDC)

The trapping and long term retention of exogenous or autogenous antigens in the form of immune complex (IC) is one of major cardinal features of follicular dendritic cells (FDC). This tapping are thought to be mediated mainly by complement receptors (C’Rs), which are distributed abundantly on the surface of FDC1,2. The precise molecular mechanisms of this phenomenon, however, are still obscure. For example, controversial ideas have been reported as to the contribution of Fc-receptors (FcRs) to the trapping3,4,5. Especially the investigations are very limited in human system because it is difficult to establish the experimental approaches in vivo.

Successful resection of a liver metastasis from gastric leiomyoblastoma: report of a case.

A 20-year-old woman was referred to our hospital for detailed investigation of a gastric submucosal tumor. A leiomyoma was preoperatively diagnosed and laparoscopic-assisted enucleation was performed. The resected tumor was 4 × 3 × 1.5 cm in size and postoperative histological examination identified it as a gastric leiomyoblastoma. Therefore, a secondary resection in the form of a distal gastrectomy was carried out. No tumor cells were found in the gastric specimen or in the lymph nodes; however, 5 months after the operation, an abdominal computed tomography scan revealed a recurrence in the liver, and she was readmitted for further examinations. The lesion was diagnosed as a single liver metastasis from the gastric leiomyoblastoma and successfully resected. The histopathological findings of the liver tumor resembled those of the primary gastric tumor. Her postoperative course was uneventful and she has been well, without any evidence of recurrence, to date. Only 12 other cases of leiomyoblastoma of the stomach with liver metastasis have been reported in Japan, all of which were associated with a very poor prognosis. Therefore, patients with this unusual disease entity should be carefully followed up after resection of the primary tumor.

Expression of Musashi-1 Antigen, A Neural Stem Cell RNA-Binding Protein, in the Liver Tissues of Patients with Hepatitis

Musashi-1 is a gene encoding the RNA-binding protein involved in regulating asymmetrical division in neural stem cells. As Musashi-1 antigen (Msi-1) can be a potent marker for liver stem cells, we used it as an immunological tool to investigate the mechanisms involved in liver reconstruction after injury. The expression of CD 68 antigen (CD 68), a marker for macrophages, was also analyzed. Immunohistochemical studies were performed on liver biopsy specimens from patients with various liver diseases, including 9 with acute hepatitis, 13 with chronic hepatitis, and 5 with liver cirrhosis. Msi-1 was expressed predominantly in the cytoplasm of CD 68-positive macrophages, which have the potential for activation or are already activated. These cells were found in necrotic or inflamed parenchyma or in the portal area, especially in the acute hepatitis specimens. Most of the Kupffer cells (resident liver macrophages) were located in non inflamed areas and were positive for CD 68 but negative for Msi-1. We also observed Msi-1 expression on oval-shaped cells in the inflamed portal area, although further analysis is necessary to determine whether these cells were liver stem cells. The asymmetrical division that occurs in such stem cells and is regulated by Msi-1 may playa role in promoting recovery from hepatitis and subsequent reconstruction of the liver by activating the mononuclear phagocyte system, as well as by replacing damaged liver cells with new ones derived from stem cells.

An Immunohistochemical Study on Isotypes of the Immune Complexes Trapped by Follicular Dendritic Cells (FDC) in Various Human Lymphoid Tissues

Follicular dendritic cells (FDC) are well known to trap and retain immune complexes (IC) containing various isotypes of immunoglobulins1,2,3. In addition, it has been reported that FDC retained IC with peculiar isotypes of immunoglobulins in certain diseases (IgAl in IgA nephropathy4,5, IgE in Kimura’s disease6 etc). These observations imply the particular relationships between isotype of the immunoglobulin constituting IC retained by FDC and immune responses or pathogenesis of certain immunopathological conditions. In the present study, distribution of each isotype of immunoglobulins was systemically examined in human various lymphoid tissues using immunohistochemical techniques with special reference to the reactivity within germinal centers (GC).