Health Effects of Drinking Water Produced from Deep Sea Water: A Randomized Double-Blind Controlled Trial

Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU (n = 41) or mineral water (control) groups (n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.     

Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia

Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.     

A case of intraductal tubulopapillary neoplasm of pancreas with severe calcification,a potential pitfall in diagnostic imaging

We experienced a case of intraductal tubulopapillary neoplasms (ITPN) of the pancreas with severe calcification, which complicated image diagnosis. A pancreas head tumor was detected in a Japanese female in her 50s. Early enhancement by contrast‐enhanced CT and coarse calcification suggested a neuroendocrine tumor, although the obstruction and dilation of the main pancreatic duct appeared to be an intraductal tumor. An endoscopic ultrasound‐guided fine needle aspiration biopsy specimen revealed adenocarcinoma tissue. Pancreaticoduodenectomy was performed, and the patient has been well without evidence of recurrence for over 10 months. Pathological examination on the resected specimen revealed that the tumor showed papillary and tubulo‐cribriform growth patterns. Together with typical immunohistochemical results, the final diagnosis of ITPN was made. Characteristically, this case showed extensive calcification of both psammoma body‐type and non psammoma body‐type with foamy macrophage aggregation. This is the first report of ITPN with two types of calcification and macrophage. Since calcification might be one of the characteristic histological findings in ITPN as shown in our case, the possibility of ITPN should be also considered when calcification is detected in pancreatic lesions by various imaging modalities.     

Membranous nephropathy associated with thyroid-peroxidase antigen

A 6-year-old previously healthy Japanese girl was found to have dipstick 2+ proteinuria and a goiter based on the results of a routine school medical examination. Her serum free-thyroxine level was 4.98 ng/dL (normal range 0.95–1.74 ng/dL), thyroid-stimulating hormone (TSH) was less than 0.003 μU/mL (0.34–3.88 μU/mL), anti-microsomal (anti-thyroid-peroxidase) antibody was 1600 T (up to 100), anti-thyroglobulin antibody was 400 T (up to 100), and TSH-receptor antibody was 84% (up to ±10%). These results are consistent with a diagnosis of Graves’ disease. Electron microscopy examination of a renal biopsy specimen revealed electron-dense deposits located in the subepithelial spaces, and immunofluorescence microscopy examination demonstrated bright granular stainings of immunoglobulin G along the glomerular capillary walls. These findings are characteristic of membranous nephropathy. To investigate the relationship between the membranous nephropathy and Graves’ disease, we carried out a second immunofluorescence study, which revealed that the immunoglobulin G granular deposits corresponded to glomerular granular staining of thyroid-peroxidase, whereas staining for thyroglobulin was absent. It was therefore assumed that the deposition of immune complexes mediated by thyroid-peroxidase had caused the membranous nephropathy in this patient. This is the first report of membranous nephropathy associated with Graves’ disease in which deposits of thyroid-peroxidase, rather than thyroglobulin, have been confirmed in the kidney. This study was presented in the 14th congress of International Pediatric Nephrology Association (IPNA), Budapest, Hungary, 2007.     

Omission of mediastinal lymph node dissection in lung cancer: its techniques and diagnostic procedures.

To reduce or omit a mediastinal lymph node dissection in the patients with clinical stage I non-small cell lung cancer (NSCLC), several authors examined the prevalence of metastatic sites of lymph nodes. Because lymphatic drainage usually heads for the upper mediastinum in upper lobe cancer and for the lower mediastinum in lower lobe cancer, upper and lower mediastinal lymph node dissection could be reduced in lung cancers of lower lobe and upper lobe. By using sentinel node (SN) navigation surgery, it is possible to omit mediastinal lymph node dissection. Radiological findings are also useful to determine reduction of mediastinal lymph node dissection. In clinical stage Ia adenocarcinomas that show ground glass opacity (GGO) findings on computed tomography (CT) or negative for fluorodeoxyglucose accumulation on positron emission tomography (PET), mediastinal lymph node dissection can be omitted, because these types of adenocarcinomas rarely metastasize to the lymph nodes. By using these procedures, mediastinal lymph node dissection can be reduced or omitted with little risk of local recurrence.     

Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.