Ultrasound-guided lung biopsy with coaxial technique: pleural contact length affects the occurrence of pneumothorax after first puncture.

PURPOSE: To assess prebiopsy characteristics influencing the occurrence of pneumothorax after first puncture of ultrasound (US)-guided lung biopsy with coaxial technique. MATERIALS AND METHODS: From January 2007 to September 2018, 180 peripheral lung lesions in 174 patients who underwent B-mode US-guided lung biopsy with coaxial technique at single institution were included in this study. Technical success was defined as the ability to make a diagnosis using the acquired sample with/without an adverse event of pneumothorax. Statistical analyses of prebiopsy characteristics were performed to identify the most important cutpoint and to evaluate the effect on diagnostic accuracy. RESULTS: Of the 180 lesions (mean size, 37 mm ± 26.2; mean pleural contact length, 38.2 mm ± 34.4), technical success rate was 97.2% (175/180 lesions) and diagnostic accuracy rate was 91.6% (165/180 lesions). Pneumothorax occurred immediately after first puncture for seven of 180 lesions. Classification and regression tree analysis and Fisher's exact test showed the proportion of the pneumothorax immediately after first puncture was higher in lesions with pleural contact length less than 9.78 mm (p = 0.002). No significant difference was shown between the pneumothorax and non-pneumothorax after first puncture in technical success and final diagnosis success rate. CONCLUSION: Pleural contact length affects the occurrence of pneumothorax after first puncture of US-guided lung biopsy with coaxial technique.

Establishment of immunity against Epstein-Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion.

CHARGE syndrome is a rare congenital malformation syndrome which may share symptoms with DiGeorge syndrome. Complete DiGeorge syndrome (cDGS) is a severe form of DiGeorge syndrome, characterized by a CD3+ T-cell count of <50/mm3 due to athymia, and is fatal without immunologic intervention. We performed peripheral blood lymphocyte transfusion (PBLT) from an HLA-identical sibling without pretransplant conditioning in a CHARGE/cDGS patient with a novel CHD7 splice site mutation. Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis, and neither acute nor chronic GVHD was observed. After PBLT, T-cell proliferative response to phytohemagglutinin and concanavalin A recovered, and intractable diarrhea improved. EBV infection, evidenced by a gradual increase in the viral genome copy number to a maximum of 2861 copies/µgDNA on day 42 after PBLT, resolved spontaneously. HLA A2402 restricted, EBV-specific CTLs were detected from peripheral blood on day 148, and EBV seroconversion was observed on day 181. Thus, EBV-specific immunity was successfully established by PBLT. Our results indicate that PBLT is a simple and effective therapy to reconstitute immune systems in CHARGE/DiGeorge syndrome.

[A Case of Extrahepatic Bile Duct Carcinoid Tumor Involving Diagnostic Difficulties].

A patient in his 60s had undergone laparoscopic anterior resection for the treatment of carcinoma of the rectum in February 2016. Histopathologic examination revealed the lesion as a pT2(MP)n(-)M0, fStage Ⅰrectal cancer. One year post-surgery, contrast-enhanced computed tomography(CT)revealed enhancement of parts of the intrapancreatic distal bile ducts. Magnetic resonance cholangiopancreatography(MRCP)showed filling defects at the same site. Magnetic resonance imaging( MRI)with an endorectal coil(ERC)was then performed to identify reproducible bile duct filling defects. Neither cytology nor biopsy yielded any findings that definitely indicated malignancy. Intraductal ultrasonography(IDUS)led to the suspicion of a nonepithelial tumor or an enlarged lymph node. Repeated biopsies via ERC were performed based on the absence of evidence of malignancy and revealed the presence of some atypical cells within the lesions. Although no definitive diagnosis could be made, the patient was scheduled for surgery in June 2017 after obtaining his consent. Upon taping of the common bile duct during surgery, a tumor was palpable on the dorsal aspect of the pancreas. The bile duct tumor was completely excised and submitted for intraoperative diagnosis; the pancreatic dorsal aspect appeared to be totally split. There was no evidence of atypia in the neoplasm, which was therefore considered to be benign; however, malignancy could not be completely ruled out because the patient had presented with elevated serum levels of carbohydrate antigen(CA)19-9 once before the operation. After intraoperative consultation with the patient's family members, who were reluctant to provide consent for pancreaticoduodenectomy, we completed the operation with resection of the bile duct tumor, followed by choledochojejunostomy. The tumor was found to be chromogranin A(+), cluster of differentiation(CD)56(+/-), CA19-9(+, solely ductal structure), carcinoembryonic antigen(CEA)(+, solely ductal structure), and intranuclear p53(-), with an MIB- 1 index of<2%. With regard to neuroendocrine markers, a region that could potentially have been a carcinoid tumor, based on the findings on hematoxylin and eosin(HE)staining, and a lumenized superficial region showed positivity in toto. Therefore, the lesion as a whole was diagnosed as a G1 carcinoid neuroendocrine tumor(NET). However, the superficial lumenized layer was positive for both CA19-9 and CEA; therefore, the tumor was thought to concurrently have epithelial characteristics. The lateral stumpwas negative, while the status of the ablated region remained unclear. After discussing the histopathologic examination results with the patient and his family members, the patient's follow-upwas decided to consist of periodic checkups without any further surgical intervention. The patient has since remained free of recurrence. Carcinoid tumor of the bile duct is extremely rare but should be considered in cases involving bile duct tumors that show enhancement on imaging prior to surgery and for which no definitive diagnosis can be established despite repeated biopsy explorations.

Rapidly progressive renal failure due to tubulointerstitial infiltration of peripheral T-cell lymphoma, not otherwise specified accompanied by uveitis: a case report.

BACKGROUND: Rapid decline in renal dysfunction due to primary renal lymphoma, or secondary renal lymphoma by infiltration from a primary origin, is extremely rare. There are notably few reports indicating infiltration of T-cell lymphoma into the kidney. CASE PRESENTATION: A 61-year-old woman with a sudden body rash and liver dysfunction was brought to our hospital presenting with a dull headache and blurred vision. Laboratory tests revealed rapidly progressive renal failure. Histological examination of the kidney and skin indicated infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Infiltration of PTCL-NOS to the liver and spleen, and presence of Uveitis masquerade syndrome were suspected. Imaging showed that the lesion was limited to extralymphatic organs. Renal function was improved with administration of steroids, including pulse steroid therapy, before administering cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. CONCLUSIONS: This is the first reported case of rapidly progressive renal failure caused by perivascular tubulointerstitial nephritis with the direct invasion of PTCL-NOS. In our case, a single steroid dose showed dramatic results with respect to renal symptoms.

Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis (AAV) Restricted to the Limbs.

A previously healthy 58-year-old man was admitted for muscle pain and weakness [manual muscle testing (MMT) of 4/4 for upper and lower limbs]. We detected elevated levels of inflammatory makers and PR3-anti-neutrophil cytoplasmic antibody (ANCA). Subsequently, the muscle weakness rapidly progressed to an MMT of 2 for all limbs. Magnetic resonance imaging indicated muscle edema, and the creatine kinase (CK) level increased to 29,998 U/L. Methylprednisolone (mPSL) and cyclophosphamide pulse therapy improved the patient symptoms. MMT recovered to 4 for all limbs. A muscle biopsy showed degenerated muscle fibers surrounded by neutrophil-predominant infiltration. In addition, lamina elastic breakdown and fibrinoid necrosis of arterioles were observed. A final diagnosis of microscopic polyangiitis (MPA) limited to the muscles was made.

[A Case of Complete Response to Computed Tomography-Guided Celiac Plexus Neurolysis of Pain Associated with Postoperative Recurrence of Colon Cancer].

The patient was a man in his 40s, who had undergone laparoscopic ileocecal resection with lymph node dissection(D3)for cecal cancer in January 2012. Histopathological examination of the resected specimens had revealed StageⅡ primary tumor with subserosal invasion and positive metastasis in 1-3 regional lymph nodes(pT2[SS]n1[+]). The pathological stage was Ⅲa(fStage Ⅲa), and the tumor showed RAS gene mutation. The patient was administered 5 cycles of postoperative adjuvant chemotherapy with oral tegafur/uracil(UFT)in combination with calcium folinate(UZEL). Abdominal computed tomography( CT)performed 1.5 years postoperatively revealed liver metastasis, and a laparoscopic partial hepatectomy was performed in August 2015. In addition, a node in the greater omentum, located in the inferior surface of the liver, was also resected. Histopathological examination of the resected specimens revealed peritoneal metastasis, based on the identification of the same type of adenocarcinoma as the colon cancer. The patient was given 8 cycles of adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Then, he presented with colonic ileus, caused by recurrent dissemination, and underwent a laparoscopic transverse colectomy in October 2015. Multiple perineal disseminations were found intraoperatively, and chemotherapy was initiated with irinotecan plus tegafur/gimeracil/oteracil(S-1)plus bevacizumab(IRIS/BV)for the recurrent and unresectable disease. After 27 cycles of this regimen, lung metastasis was detected; in addition, progression of the para-aortic node metastasis around the celiac plexus was also observed, and the patient was considered as having pro- gressive disease(PD). Treatment with trifluridine/tipiracil(TAS102)was started in September 2017. Prior to the initiation of this regimen, the dose of opioid rescue medication previously started for back and abdominal pain was rapidly increased. Accordingly, the base dose was increased, but the pain could not be controlled, and the major pain was consistently located along the area of innervation in the celiac plexus. Therefore, celiac plexus neurolysis(CPN)was performed as a local therapy. A CT-guided injection technique was used to administer urografin, bupivacaine, and absolute ethanol to complete the procedure. The patient was discharged without major complications, and the base opioid dose was gradually reduced. Since the patient did not require any rescue medication during daytime on some days, the reduction of the base opioid dose was significantly effective in improving the patient's quality of life(QOL). In patients with pain possibly caused by metastasis to the para-aortic nodes, this local therapy technique may be considered.

Quantification of bleeding volume using computed tomography and clinical complications after percutaneous renal biopsy.

Background: The aim of this study was to investigate specific bleeding volume after percutaneous renal biopsy (PRB) and the correlation between bleeding volume and clinical parameters. Methods: A retrospective study of 252 consecutive patients (153 male patients and 99 female patients) who underwent PRB at the Department of Nephrology, Japanese Red Cross Ishinomaki Hospital, between July 2013 and January 2016 was conducted. PRB was performed under ultrasound guidance using an automated spring-loaded biopsy device and a 16-cm, 16-gauge needle. Patients underwent computed tomography (CT) the day after PRB. Bleeding volume after PRB was evaluated using reconstructed CT data. Results: The median bleeding volume after PRB was 38 mL (25th-75th percentile, 18-85 mL), with ≥4 punctures identified as a risk factor for massive bleeding. The incidence rates of macrohematuria, transient hypotension and bladder obstruction were 14.3, 8.7 and 4.7%, respectively. Post-PRB blood transfusion and intervention were required in 4.7 and 0.8% of patients, respectively. Conclusion: Although it is difficult to assess the risk for massive bleeding prior to PRB, we do provide evidence of a specific increased risk with ≥4 puncture attempts, and recommend careful follow-up of these patients.

Perirenal fat stranding is not a powerful diagnostic tool for acute pyelonephritis.

PURPOSE: Pyelonephritis, an upper urinary tract infection, is a serious infection that often requires hospitalization. However, the accurate diagnosis of acute pyelonephritis can be difficult, especially among older individuals who can present with unusual symptoms. Imaging with computed tomography (CT) is not unusual in the diagnosis of pyelonephritis, with some clinicians regarding perirenal fat stranding (PFS) as a characteristic finding. However, the sensitivity and specificity of PFS in diagnosing pyelonephritis are currently unknown. We therefore sought to clarify the relevance of PFS in diagnosing acute pyelonephritis. PATIENTS AND METHODS: We conducted a case-controlled retrospective analysis of medical records. The pyelonephritis group included 89 patients who had been diagnosed with acute pyelonephritis, while the control group included 319 patients who had undergone percutaneous renal biopsy. CT findings were available for both groups. The frequency of PFS and its sensitivity and specificity for the diagnosis of acute pyelonephritis were investigated. RESULTS: The mean ages of the pyelonephritis and control groups were 74±15 years and 63±16 years, respectively. A total of 28% of men were in the pyelonephritis group vs 61% of men in the control group. The frequency of PFS was 72% in the pyelonephritis group vs 39% in the control group. Age and renal dysfunction were associated with an increased frequency of PFS. After adjusting for age, sex, and renal function using a propensity score analysis, the sensitivity, specificity, and positive likelihood ratio of PFS for diagnosing acute pyelonephritis were 72%, 58%, and 1.7, respectively. CONCLUSION: The presence of PFS was not useful in diagnosing acute pyelonephritis.

Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m2/week for 4 weeks (i.e., the conventional lymphoma dosing schedule) is used, but the optimal dosing schedule is controversial. Indeed, a single-dose of RTX successfully controlled nephrotic syndrome. However, to date, the effectiveness of a single RTX dose in treating MPA has not been fully investigated in Japan. This was a retrospective observational study. Six newly diagnosed patients with MPA were initially treated with methylprednisolone and a single dose of RTX (375 mg/m2). We investigated the patients' clinical features, as well as the efficacy and safety of RTX treatment. All patients attained remission on a tapered prednisolone dose of < 10 mg/day during the first 12 months. One patient relapsed after 12 months whereas another required hospitalization owing to infective spondyloarthritis. Adverse reactions to RTX infusion and late-onset neutropenia were not observed. Therefore, a single-dose treatment with RTX induced remission with few complications, and allowed tapering the prednisolone treatment. We conclude that a single dose of RTX is a promising induction therapy for MPA, reducing the cost associated with multiple doses.

IgG4-Related Disease Manifesting as Interstitial Nephritis Accompanied by Hypophysitis.

BACKGROUND IgG4-related disease is a systemic disease with marked infiltration of IgG4-positive plasma cells into affected organs and elevated serum IgG4. On clinical examination, swelling, nodules, and hypertrophic lesions might appear simultaneously or metachronously in different organs. CASE REPORT An 85-year-old man with sudden-onset polydipsia and polyuria insipidus was transported to our hospital because of hypothermia and general malaise. Laboratory tests revealed renal failure and central diabetes insipidus. According to his serum IgG4 level, the patient was diagnosed with possible IgG4-related kidney disease accompanied by IgG4-related hypophysitis. Abdominal contrast-enhanced computed tomography, hypophysis magnetic resonance imaging, and histological examination of the kidney were performed. Glucocorticoid therapy was administered and his renal function improved gradually. However, his central diabetes insipidus did not improve. CONCLUSIONS Glucocorticoid therapy showed different therapeutic effects on the kidney and posterior lobe of the hypophysis. It is possible that glucocorticoid therapy needs to be supported by other immunomodulatory therapies to have an effect on all affected organs.

Renal infarct volume and renal function decline in acute and chronic phases.

BACKGROUND: Acute renal infarction (ARI) is a rare disease. ARI causes decline in renal function in both the acute and chronic phases. However, the correlation between the volume of the infarction and degree of renal function decline has not been fully investigated. Therefore, we aimed to examine the relationship between the volume of the infarction and degree of renal function decline. METHODS: We performed a single-center, retrospective, observational study investigating clinical parameters and the volume of the infarction. The volume of the infarction was measured using reconstructed computed tomography data. RESULTS: A total of 39 patients (mean age, 72.6 ± 13.2 years; men, 59%) were enrolled. The median infarction volume was 45 mL (interquartile range, 14-91 mL). The volume of the infarction was significantly associated with the peak lactate dehydrogenase (LDH) level (median, 728 IU/L; interquartile range, 491-1227 U/L) (r = 0.58, p < 0.01) and the degree of renal function decline in both acute and chronic phases (r = -0.44, -0.38, respectively, p < 0.05). The peak LDH level was significantly correlated with the degree of renal function decline in the acute phase but not in the chronic phase (r = -0.35, -0.21; p < 0.05, N.S., respectively). CONCLUSIONS: The volume of the infarction may be a factor in the degree of renal function decline in ARI. Therefore, assessment of infarct volume in ARI is important.

ER stress response in NG108-15 cells involves upregulation of syntaxin 5 expression and reduced amyloid ß peptide secretion.

Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of neurodegenerative diseases such as Alzheimer׳s disease (AD). We previously showed that manipulation of the ER-Golgi-soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (ER-Golgi SNARE) syntaxin 5 (Syx5) causes changes in Golgi morphology and the processing of AD-related proteins. To understand the pathophysiologic significance of these phenomena, we examined whether the expression of Syx5 is altered by ER stress. De novo synthesis of ER-Golgi SNARE Syx5 and Bet1 was induced by various ER stressors. Elevated expression of Syx5 and Bet1 was associated with increased levels of these proteins in vesicular components, including ER-Golgi-intermediate-compartment/vesicular tubular clusters. In addition, ER stress diminished amyloid ß (Aß) peptide secretion. Knockdown of Syx5 expression enhanced the secretion of Aß peptides under condition without ER stress. Moreover, diminished Aß peptide secretion resulting from ER stress was significantly reversed by Syx5 knockdown. These findings suggest that Syx5 plays important roles in ß-amyloid precursor protein processing and in the ER stress response that precedes apoptotic cell death and may be involved in the crosstalk between these two pathways.

[Usefulness of ursodeoxycholic acid in a case of hepatic sarciodosis].

A 38-year-old man was admitted to our hospital with a diagnosis of pulmonary sarcoidosis accompanied with elevated biliary enzyme levels. Various imaging modalities, and percutaneous liver biopsy confirmed the diagnosis of hepatic sarcoidosis. Abnormalities of biliary enzymes improved after the administration of ursodeoxycholic acid (UDCA). In this case, the mechanism of pharmacologic action was considered to be the glucocorticoid-like effect of UDCA. UDCA might be a therapeutic option for hepatic sarcoidosis without general symptoms.

The trehalose transporter 1 gene sequence is conserved in insects and encodes proteins with different kinetic properties involved in trehalose import into peripheral tissues.

We recently cloned a trehalose transporter gene (Tret1) that contributes to anhydrobiosis induction in the sleeping chironomid Polypedilum vanderplanki Hinton. Because trehalose is the main haemolymph sugar in most insects, they might possess Tret1 orthologs involved in maintaining haemolymph trehalose levels. We cloned Tret1 orthologs from four species in three insect orders. The similarities of the amino acid sequence to TRET1 in P. vanderplanki were 58.5-80.4%. Phylogenetic analysis suggested the Tret1 sequences were conserved in insects. The Xenopus oocyte expression system showed apparent differences in the K(m) and V(max) values for trehalose transport activity among the six proteins encoded by the corresponding orthologs. The TRET1 orthologs of Anopheles gambiae (K(m): 45.74 +/- 3.58 mM) and Bombyx mori (71.58 +/- 6.45 mM) showed low trehalose affinity, whereas those of Apis mellifera (9.42 +/- 2.37 mM) and Drosophila melanogaster (10.94 +/- 7.70 mM) showed high affinity. This difference in kinetics might be reflected in the haemolymph trehalose:glucose ratio of each species. Tret1 was expressed not only in the fat body but also in muscle and testis. These findings suggest that insect TRET1 is responsible for the release of trehalose from the fat body and the incorporation of trehalose into other tissues that require a carbon source, thereby regulating trehalose levels in the haemolymph.

Analysis of prognostic factors in patients with gastric varices after endoscopic treatment.

BACKGROUND: The prognostic factors, including gastric variceal bleeding itself, in patients with gastric varices (GV) after endoscopic treatment remain unclear. The aim of this study was to analyze prognostic factors in patients with GV after endoscopic treatment as well as to evaluate safety and efficacy of our endoscopic treatment. PATIENTS AND METHODS: This study enrolled 115 patients who underwent endoscopic treatment for GV between October 1988 and December 2003 using cyanoacrylate and 5% ethanolamine oleate. Successful hemostasis, recurrence rates, rebleeding rates, survival rates, complications and prognostic factors after the treatment were retrospectively reviewed. RESULTS: Treatment sessions for GV were performed 3.4 +/- 2.5 times. All cases, including 14 emergency cases, were treated successfully. The cumulative recurrence rates at 1, 3 and 5 years after the treatment were 7.0%, 15.6% and 20.0%, respectively, and the cumulative rebleeding rates at 1, 3 and 5 years were 3.5%, 8.7% and 14.8%, respectively. The overall survival rates were 78.3%, 63.7% and 51.5% at 1, 3 and 5 years, respectively. Grade B or C in Child-Pugh classification, emergency or elective cases, and association with hepatocellular carcinoma were identified as significant negative prognostic factors after endoscopic treatment by multivariate analysis. Although several complications were observed, there was no mortality. CONCLUSIONS: Grade B or C in Child-Pugh classification, emergency or elective situation, and association with hepatocellular carcinoma are negative prognostic factors after endoscopic treatment.

[Xanthogranulomatous cholecystitis associated with a suspicious colonic fistula and its spontaneous resolution].

Fistula between the gallbladder and colon is a rare condition. Even more infrequent is spontaneous resolution of the fistula. We encountered a case of cholecystocolic fistula associated with xanthogranulomatous cholecystitis (XGC) that was diagnosed definitively using CT, MRI, and colonoscopy. An 82-year-old woman with no remarkable medical history presented with fever and right hypochondralgia that had continued for 8 days. Abdominal ultrasound showed a hyperechoic area as air in the lumen of the gallbladder with a hypertrophic wall. Contrast-enhanced CT, with the peripheral layer enhanced homogeneously by contrast medium, indicated air in the gallbladder with a thickened wall. Furthermore, MRI and colonoscopy revealed a fistula between the gallbladder and transverse colon strongly suggested. Those findings suggested cholecystocolic fistula associated with XGC. The patient was treated initially by administration of antibiotics, while fasting. Unfortunately, surgical specimens did not show the fistula, thus it was decided that the existence of cholecystocolic fistula with spontaneous resolution were highly suspected by the clinical course and imaging in this patient.

Dehydration-inducible changes in expression of two aquaporins in the sleeping chironomid, Polypedilum vanderplanki.

Aquaporin, AQP, is a channel protein that allows water to permeate across cell membranes. Larvae of the sleeping chironomid, Polypedilum vanderplanki, can withstand complete dehydration by entering anhydrobiosis, a state of suspended animation; however, the mechanism by which water flows out of the larval body during dehydration is still unclear. We isolated two cDNAs (PvAqp1 and PvAqp2) encoding water-selective aquaporins from the chironomid. When expressed in Xenopus oocytes, PvAQP1 and PvAQP2 facilitated permeation of water but not glycerol. Northern blots and in situ hybridization showed that expression of PvAqp1 was dehydration-inducible and ubiquitous whereas that of PvAqp2 was dehydration-repressive and fat body-specific. These data suggest distinct roles for these aquaporins in P. vanderplanki, i.e., PvAqp2 controls water homeostasis of fat body during normal conditions and PvAqp1 is involved in the removal of water during induction of anhydrobiosis.

Trehalose transporter 1, a facilitated and high-capacity trehalose transporter, allows exogenous trehalose uptake into cells.

Trehalose is potentially a useful cryo- or anhydroprotectant molecule for cells and biomolecules such as proteins and nucleotides. A major obstacle to application is that cellular membranes are impermeable to trehalose. In this study, we isolated and characterized the functions of a facilitated trehalose transporter [trehalose transporter 1 (TRET1)] from an anhydrobiotic insect, Polypedilum vanderplanki. Tret1 cDNA encodes a 504-aa protein with 12 predicted transmembrane structures. Tret1 expression was induced by either desiccation or salinity stress. Expression was predominant in the fat body and occurred concomitantly with the accumulation of trehalose, indicating that TRET1 is involved in transporting trehalose synthesized in the fat body into the hemolymph. Functional expression of TRET1 in Xenopus oocytes showed that transport activity was stereochemically specific for trehalose and independent of extracellular pH (between 4.0 and 9.0) and electrochemical membrane potential. These results indicate that TRET1 is a trehalose-specific facilitated transporter and that the direction of transport is reversible depending on the concentration gradient of trehalose. The extraordinarily high values for apparent Km (>or=100 mM) and Vmax (>or=500 pmol/min per oocyte) for trehalose both indicate that TRET1 is a high-capacity transporter of trehalose. Furthermore, TRET1 was found to function in mammalian cells, suggesting that it confers trehalose permeability on cells, including those of vertebrates as well as insects. These characteristic features imply that TRET1 in combination with trehalose has high potential for basic and practical applications in vivo.

Effect of isosorbide dinitrate on gastric blood flow in rats with liver cirrhosis determined by analyzing gastric blood flow, portal vein pressure and blood gas.

We investigated the effects of isosorbide dinitrate (IDN) on gastric blood flow (GBF), portal venous pressure (PVP) and blood gas of rats with liver cirrhosis (LC) accompanied by portal hypertension. Thirty male Wistar rats (LC in 17 and normal in 13) were used. Before and after IDN administration, GBF, PVP and blood gas in the femoral artery and portal vein were measured. Portal blood oxygen concentration was estimated by calculating the ratio of PO2 in portal blood and that in arterial blood (PpvO2/PaO2) of each rat. The GBF in the LC rats was significantly lower than that in the normal rats. In the LC group, IDN administration significantly increased the GBF. The PpvO2/PaO2 value in the group with LC was significantly lower after IDN administration than that before IDN administration. In the investigation whether changes in PVP or Ppv/PaO2 contributed more to the change in GBF after IDN administration, a significant correlation was found between rates of change in GBF and PpvO2/PaO2 were significantly correlated (r= -0.733, p <0.05). The effect of IDN on changes in the stomach accompanying portal hypertension is mainly attributable to a decrease in preload, which suppresses inflow to the stomach, as reflected by a decrease in PpvO2/ PaO2, rather than to a decrease in afterload on GBF, as reflected by a decrease in PVP.

Syntaxin 5 interacts specifically with presenilin holoproteins and affects processing of betaAPP in neuronal cells.

The specific roles of syntaxin 5 (Syx 5) in the interaction with presenilin (PS) and the accumulation of beta-amyloid precursor protein (betaAPP), as well as the secretion of beta-amyloid peptide (Abeta peptide) were examined in NG108-15 cells. Syx 5, which localizes from the endoplasmic reticulum (ER) to the Golgi, bound to PS holoproteins, while the other Syxs studied did not. Among familial Alzheimer's disease (FAD)-linked PS mutants, PS1deltaE9, which lacks the endoproteolytic cleavage site, showed markedly decreased binding to Syx 5. The interaction domains in Syx 5 were mapped to the transmembrane region and to the cytoplasmic region containing the alpha-helical domains, which are distinct from the H3 (SNARE motif). Among all of the Syxs examined, only overexpression of Syx 5 resulted in the accumulation of betaAPP in the ER to cis-Golgi compartment, an attenuation of the amount of the C-terminal fragment (APP-CTF) of betaAPP, and a reduction in the secretion of Abeta peptides. Furthermore, co-expression of Syx 5 with C99 resulted in an increase in APP-CTF and suppressed Abeta secretion. Taken together, these results indicate that Syx 5 may play a specific role in the modulation of processing and/or trafficking of FAD-related proteins in neuronal cells by interaction with PS holoproteins in the early secretory compartment of neuronal cells.