Biography:

In the past Fumio Nomura has collaborated on articles with Kunihiko Ohnishi and Hidetaka Terabayashi. One of their most recent publications is Case reportAneurysm of the intrahepatic branch of the portal vein: Report of two cases☆. Which was published in journal Gastroenterology.

More information about Fumio Nomura research including statistics on their citations can be found on their Copernicus Academic profile page.

Fumio Nomura's Articles: (19)

Case reportAneurysm of the intrahepatic branch of the portal vein: Report of two cases☆

AbstractTwo patients in whom real-time ultrasonography and percutaneous transhepatic portography or the venous phase of the arteriogram of the superior mesenteric artery demonstrated a localized saccular dilation of a peripheral branch of the portal vein are described. One patient subsequently died, and autopsy confirmed the diagnosis. A hypoechoic lesion continuous with a branch of the portal vein seems to be the characteristic sonographic picture. Radiologic evidence for portal vein aneurysm was obtained in only 2 of 300 patients with portal hypertension in whom percutaneous transhepatic portography was performed, and in 2 of 3000 patients who visited our unit and in whom ultrasonography for the liver was performed. Thus, aneurysm of the intrahepatic portal vein does occur, but very rarely.

Case reportTransformation of inferior vena caval thrombosis to membranous obstruction in a patient with the lupus anticoagulant

AbstractA 24-yr-old woman with hemolytic anemia developed multiple thrombosis of the hepatic vein and inferior vena cava. She was found to have circulating lupus anticoagulant that could have been causally related to the thrombosis and hence the Budd-Chiari syndrome. On her first admission to the hospital vena cava and hepatic vein catheterizations revealed partial thrombotic occlusion of the cava at the level of the diaphragm, which was subsequently transformed into complete membranous obstruction. The right hepatic vein, which was patent on the first admission, was also completely occluded. These observations support the theory that membranous obstruction of the inferior vena cava is a sequela to inferior vena caval thrombosis rather than a congenital anomaly.

Quantitative aspects of portal-systemic and arteriovenous shunts within the liver in cirrhosis

AbstractTo estimate vascular changes in chronic liver disease, we quantitated intrahepatic arteriovenous and portal-systemic shunts in 12 patients with cirrhosis and arteriovenous shunts alone in 4 patients with cirrhosis. An index was obtained for intrahepatic arteriovenous shunts by instilling technetium 99m-macroaggregated albumin into the proper hepatic artery and portal-systemic shunts, by the same procedure done in the portal trunk, near the porta hepatis on different days. Counts were taken over the liver and both lungs in the anterior as well as the posterior view for calculation of the shunt index: cpm in lungs ÷ cpm in liver and lungs × 100%. In the 12 patients with cirrhosis in whom both shunts were measured, intrahepatic arteriovenous shunting was significantly lower compared with intrahepatic portal-systemic shunting (1.4% ± 1.1% vs. 36.0% ± 29.0%, p < 0.001). Thus, it seems that in patients with cirrhosis, the development of intrahepatic arteriovenous shunts is not as great as that of portalsystemic shunts, which were found in this study to be considerable and variable in degree.

Portal venous hemodynamics in hepatocellular carcinoma: Effects of hepatic artery embolization

AbstractPortal hemodynamics were studied in 55 patients with hepatocellular carcinoma in comparison with 41 normal subjects, using the duplex system that consists of an electronic sector scanner and a pulsed Doppler velocitometer. Changes of portal hemodynamics after transcatheter hepatic artery embolization were also investigated in 15 of the patients with hepatocellular carcinoma. The duplex system showed that 9 of the 55 had no Doppler signal in the portal trunk, suggesting portal vein thrombosis, 2 had hepatofugal flow in the portal trunk indicative of arterioportal shunts, and 44 had hepatopetal flow in the portal trunk. One of the 9 patients with no significant portal venous flow showed hepatopetal flow in collateral veins at the porta hepatis, suggesting cavernous transformation of the portal vein. All of these ultrasound findings were confirmed by subsequent celiac-mesenteric angiography. In 44 of the 55 patients there was no tumor invasion in the portal trunk, and portal venous flow was found to be close to that of normal subjects regardless of the stage or size of tumor, and tumor invasion into relatively large portal branches. After transcatheter hepatic artery embolization, portal venous flow was increased, even on the next day, and it remained increased for at least 2 wk. Thus, the duplex system is useful to study qualitative and quantitative changes of portal hemodynamics in hepatocellular carcinoma. Our observations suggest that the portal venous flow is kept relatively constant by some homeostatic mechanism even in advanced hepatocellular carcinoma until the tumor invades into the portal trunk, and that it increases when hepatic arterial flow is occluded.

Ultrasonic doppler studies of hepatocellular carcinoma and comparison with other hepatic focal lesions

AbstractOne hundred fifty-four liver lesions, including 63 hepatocellular carcinomas, were studied to determine the value of duplex ultrasound in the diagnosis of small hepatocellular carcinomas. Arterial Doppler signals were obtained either within the body of the tumor, at its periphery, or in both locations, from 28 of 37 hepatocellular carcinomas ≤3 cm in diameter and from all 26 hepatocellular carcinomas with a diameter >3 cm. Arterial Doppler signals were obtained at the periphery of 5 of 7 cholangiocarcinomas, 4 of 11 liver metastatic tumors, and 5 of 23 hemangiomas. No such signals were obtained from 29 regenerative nodules, 10 hepatic pseudotumors, and 11 liver cysts. The mean peak systolic frequency seen in hepatocellular carcinoma (1.2 kHz) was significantly greater than in cholangiocarcinoma (0.6 kHz), metastatic tumors (0.5 kHz), or hemangiomas (0.3 kHz). A peak systolic frequency of >3 kHz was found in 6 of 8 hepatocellular carcinomas ≥4 cm in diameter with angiographically proven arterioportal shunting, whereas the value in other hepatocellular carcinomas or other hepatic focal lesions was <2.6 kHz. This study showed that the peak systolic shift was related to the degree of arterioportal shunting. Because shunting is either minor or nonexistent in small hepatocellular carcinomas, the value of duplex Doppler ultrasound in the diagnosis of these lesions appears to be limited.

Original ContributionsSerum des-gamma-carboxy prothrombin levels determined by a new generation of sensitive immunoassays in patients with small-sized hepatocellular carcinoma

AbstractOBJECTIVE:Des-gamma-carboxy prothrombin (DCP), also called protein induced by vitamin K absence or antagonist II (PIVKA-II), is a tumor marker complementary to AFP for the diagnosis of hepatocellular carcinoma (HCC). Currently available immunoassays for DCP are not sensitive enough to detect HCC at an early stage. Recently, two new immunoassays with enhanced sensitivity were developed. The aim of this study was to assess the diagnostic values of the new methods in patients with small-sized HCC.METHODS:Coded serum samples obtained from 36 patients with small-sized and single-nodular HCC (≤3 cm in diameter) and 49 patients with posthepatitic cirrhosis not carrying HCC were analyzed. DCP levels were determined in three different ways: 1) conventional EIA; 2) a new immunoassay using the electrochemiluminescence (ECLIA) detection system; and 3) a new immunoradiometric assay (IRMA). Lectin-reactive profiles of AFP (AFP-L3) were also determined.RESULTS:In 36 patients with small-sized HCC, the rates of abnormal values obtained by the conventional, ECLIA, and IRMA methods were 2.7%, 27.8%, and 16.7%, respectively. An ROC analysis of the two new methods (ECLIA vs IRMA) revealed a better performance by the ECLIA method (p < 0.05). The true positive rate of AFP-L3 was 22.2%, whereas a combination assay of ECLIA for DCP and AFP-L3 resulted in a 41.7% sensitivity with a specificity of 90%.CONCLUSIONS:Compared with the conventional method, the sensitivity in detecting small-sized HCC was increased in the two new DCP immunoassays (ECLIA and IRMA). The overall performance as evaluated by an ROC analysis was significantly better in ECLIA than in IRMA.

Application of Fourier-transform infrared (FT-IR) spectroscopy for simple and easy determination of chylomicron-triglyceride and very low density lipoprotein-triglyceride

AbstractBackgroundFourier-transform infrared (FT-IR) spectroscopy is a simple and reagent-free physicochemical analysis method, and is a potential alternative to more time-consuming and labor-intensive procedures. In this study, we aimed to use FT-IR spectroscopy to determine serum concentrations of chylomicron-triglyceride (TG) and very low density lipoprotein (VLDL)-TG.MethodsWe analyzed a chylomicron fraction and VLDL fraction, which had been obtained by ultracentrifugation, to search for wavelengths to designate to each fraction. Then, partial least square (PLS) calibrations were developed using a training set of samples, for which TG concentrations had been determined by conventional procedures. Validation was conducted with another set of samples using the PLS model to predict serum TG concentrations on the basis of the samples' IR spectra. We analyzed a total of 150 samples.ResultsSerum concentrations of chylomicron-TG and VLDL-TG estimated by FT-IR spectroscopy agreed well with those obtained by the reference method (r = 0.97 for both lipoprotein fractions). FT-IR spectrometric analysis required 15 μl of serum and was completed within 1 min.ConclusionsSerum chylomicron-TG and VLDL-TG concentrations can be determined with FT-IR spectroscopy. This rapid and simple test may have a great impact on the management of patients with dyslipidemia.

Determination of serum carbohydrate-deficient transferrin by a nephelometric immunoassay for differential diagnosis of alcoholic and non-alcoholic liver diseases

Highlights•Carbohydrate-deficient transferrin (CDT) is a biomarker for alcohol abuse.•Traditional CDT assays are labor intensive hampering its wide use.•Nephelometric CDT (NCDT) assay can be easily used in clinical practice.•NCDT can detect >50% of so-called GGT non-responders.•NCDT is specific enough to exclude possible drinking in non-alcoholic liver diseases.

Lung Cancer: Clinical InvestigationsInterbronchoscopist Variability in the Diagnosis of Lung Cancer by Flexible Bronchoscopy

Study objectiveWe evaluated the interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy.Design and settingA retrospective review of the bronchoscopic records and clinical charts of patients at a university-affiliated hospital.Patients and measurementsAll records of flexible bronchoscopic procedures performed for the diagnosis of lung cancer were retrospectively reviewed, and procedures that obtained histologic or cytologic evidence of malignancy were considered positive. Rates of positivity were compared according to the following factors: operator, operator experience, bronchoscopic findings, tumor location, and tumor laterality. Factors that affected the positivity rate were evaluated using logistic regression analysis.ResultsOf 384 bronchoscopic procedures performed in 353 patients, 275 (72 percent) were positive. The positivity rate differed significantly depending on the operator (p=0.003) and the bronchoscopic findings (p<0.001). A difference between operators was noted in technically difficult cases without epithelial or subepithelial findings and when tumors were located in the upper lobe or the superior segment of the lower lobe. The bronchoscopic findings and the operator also emerged as factors significantly affecting the positivity rate in the logistic analysis.ConclusionsThe diagnostic yield of bronchoscopy for lung cancer is dependent on both the type of bronchial lesion present and the bronchoscopist.

Research ArticlePhosphorylation statuses at different residues of lamin B2, B1, and A/C dynamically and independently change throughout the cell cycle

AbstractLamins, major components of the nuclear lamina, undergo phosphorylation at multiple residues during cell cycle progression, but their detailed phosphorylation kinetics remain largely undetermined. Here, we examined changes in the phosphorylation of major phosphorylation residues (Thr14, Ser17, Ser385, Ser387, and Ser401) of lamin B2 and the homologous residues of lamin B1, A/C during the cell cycle using novel antibodies to the site-specific phosphorylation. The phosphorylation levels of these residues independently changed during the cell cycle. Thr14 and Ser17 were phosphorylated during G2/M phase to anaphase/telophase. Ser385 was persistently phosphorylated during mitosis to G1 phase, whereas Ser387 was phosphorylated discontinuously in prophase and G1 phase. Ser401 phosphorylation was enhanced in the G1/S boundary. Immunoprecipitation using the phospho-antibodies suggested that metaphase-phosphorylation at Thr14, Ser17, and Ser385 of lamins occurred simultaneously, whereas G1-phase phosphorylation at Ser385 and Ser387 occurred in distinct pools or with different timings. Additionally, we showed that lamin B2 phosphorylated at Ser17, but not Ser385, Ser387 and Ser401, was exclusively non-ionic detergent soluble, depolymerized forms in growing cells, implicating specific involvement of Ser17 phosphorylation in lamin depolymerization and nuclear envelope breakdown. These results suggest that the phosphorylations at different residues of lamins might play specific roles throughout the cell cycle.

Oncology/EndocrineAkt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells

AbstractBackgroundAlthough gemcitabine has been widely used as a first-line chemo reagent for patients with pancreatic cancer, the response rate remains low. We previously identified Annexin II as a factor involved in gemcitabine resistance against pancreatic cancer. The aims of this study were to elucidate the signaling mechanism by which Annexin II induces gemcitabine resistance and to develop a new therapy that overcomes the resistance against gemcitabine.MethodsWe compared the specific profiles of 12 targeted phosphorylated (p-) signaling proteins in gemcitabine-resistant (GEM-) and its wild-type pancreatic cancer cell lines (MIA PaCa-2) using the Bio-Plex assay system. We also evaluated the expression levels of Annexin II and two phosphoproteins, which showed different expressions in these two cell lines, by immunohistochemistry.ResultsAnnexin II overexpression was significantly associated with rapid recurrence after gemcitabine-adjuvant chemotherapy in patients with resected pancreatic cancer (P < 0.05). Bio-Plex analysis showed up-regulation of p-Akt in GEM-MIA PaCa-2 cells in which Annexin II is highly expressed. The expression level of p-Akt was significantly correlated with that of the downstream protein, p-mTOR, in pancreatic cancer tissues. Inhibition of mTOR phosphorylation canceled gemcitabine resistance in GEM-MIA PaCa-2 cells.ConclusionsThe Akt/mTOR pathway is involved in mechanisms of gemcitabine resistance induced by Annexin II in pancreatic cancer cells. This indicates that combination therapy with the mTOR inhibitor may overcome gemcitabine resistance. Annexin II as an indicator for selection of gemcitabine resistance could thus be applied to the development of novel tailor-made approaches for pancreatic cancer treatment.

Pharmacology letter Accelerated communicationEffects of natriuretic peptides (ANP, BNP, CNP) on catecholamine synthesis and TH mRNA levels in PC12 cells

AbstractAtrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are present in adrenal chromaffin cells and are co-secreted with catecholamines suggesting that these natriuretic peptides (NPs) may modulate functions of chromaffin cells in an autocrine and/or paracrine manner. Therefore, we investigated the effects of NPs on tyrosine hydroxylase (TH: a rate-limiting enzyme in biosynthesis of catecholamine) mRNA in rat pheochromocytoma PC12 cells. It was also determined whether the cyclic GMP/ cGMP-dependent protein kinase (cGMPPKG) pathway was involved in theses effects. Finally, we examined the effects of NPs on intracellular catecholamine content to confirm increase of catecholamine synthesis following TH mRNA induction. NPs (0.1 μ M) induced significant increases of the TH mRNA (ANP = BNP > CNP). Also, the effects of NPs on TH mRNA were mimicked by 8-bromo cyclic GMP (1mM) and were blocked by KT5823 (1 μ M) (inhibitor PKG) or LY-83583 (1 μM) (guanylate cyclase inhibitor). Moreover, NPs were shown to induce significant increases of intracellular catecholamine contents (ANP = BNP > CNP). These findings suggest that NPs induced increases of TH mRNA through cGMPPKG dependent mechanisms, which, in turn, resulted in stimulation of catecholamine synthesis in PC 12 cells.

Original contributionProhibitin in squamous cell carcinoma of the lung: its expression and possible clinical significance☆

Summaryrohibitin is localized to mitochondria where it might have a role in the maintenance of mitochondrial function and protection against senescence. In this study, we show that prohibitin is up-regulated in lung squamous cell carcinoma tissues compared with adjacent normal tissues using agarose 2-dimensional differential gel electrophoresis and immunoblotting. Prohibitin expression was further evaluated by immunohistochemistry. We statistically analyzed the association of prohibitin expression with clinicopathologic indicators in 78 patients with lung squamous cell carcinoma. Our data suggested that prohibitin expression was positively correlated with the International Union Against Cancer (UICC) classification of tumor grade (P < .001), pathologic stage (P < .001), tumor size (P = .01), and lymph node metastasis (P = .004). Furthermore, we found that prohibitin expression was an independent prognostic indicator (P = .037) for overall survival of patients with lung squamous cell carcinoma by multivariate analysis using the Cox regression method. These findings may encourage further studies investigating prohibitin function in lung squamous cell carcinoma.

Serum cytokine and chemokine profiles in patients with chronic inflammatory demyelinating polyneuropathy

Highlights•Serum TNF-α, HGF, MIP-1β and IL-1β levels were elevated in CIDP patients.•Serum HGF levels were increased in typical CIDP patients, but not in MADSAM.•Patients with high HGF levels showed good responses to steroid treatment.•Different cytokine profiles in the two subtypes would reflect the different pathogenesis.

Short communicationSerum cytokine and chemokine profiles in patients with juvenile muscular atrophy of distal upper extremity (Hirayama disease)

Highlights•Cytokine and chemokine profiles were analyzed in Hirayama disease.•Eotaxin, RANTES and MCP-1 serum levels were increasing in Hirayama disease.•Underlying allergic condition could be the possible cause in Hirayama disease.

Original ArticleCapsular serotyping of Haemophilus influenzae by using matrix-associated laser desorption ionization-time of flight mass spectrometry☆

AbstractHaemophilus influenzae is a major pathogenic bacteria causing invasive disease, which is classified into six capsular serotypes (a-f) and non-typeable (NT) strains. Capsular serotyping of H. influenzae is traditionally determined by serological methods and more recently by PCR methods. However, these methods are time-consuming and expensive. In the present study, matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was evaluated as an alternative method for capsular serotyping of H. influenzae clinical strains. We created an in-house database of all six serotypes and NT H. influenzae strains using the main spectrum creation standard method set to the default parameters in MADI-TOF MS. We evaluated the performance of the in-house database using 79 clinical strains already identified by PCR and 58 prospectively collected clinical strains. Measurements were performed using the Bruker MALDI BioTyper system. The peak list was matched against the reference library using the integrated pattern algorithm of the software. The best-matched spectrum was considered the serotyping result. All 137 test strains were correctly identified as H. influenzae using MALDI-TOF MS. The sensitivity and specificity for identification for type b, type e, and type f capsular serotypes and NT H. influenzae using MALDI-TOF MS were 100%/94.3%, 94.7%/97.9%, 97.4%/97.9%, and 85.5%/99.2%, respectively. Our findings indicate that MALDI-TOF MS is a useful alternative method for capsular serotyping of H. influenzae strains. This method is faster and more cost-effective than traditional methods and will therefore be useful for routine applications in clinical laboratories.

ReviewProteome-based bacterial identification using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS): A revolutionary shift in clinical diagnostic microbiology☆

Highlights•MALDI-TOF MS has made a revolutionary change in clinical microbiology.•MALDI-TOF MS is a quick and reliable method for identification of bacteria and fungi.•This technology has the potential to be used for detection of antibiotics resistance.

Data ArticleEstimated glomerular filtration rate by serum creatinine or standardized cystatin C in Japanese patients with Graves׳ disease

AbstractGlomerular filtration rate (eGFR) by serum creatinine (eGFRCr) or standardized cystatin C (eGFRCysC) were estimated in Japanese patients with Graves׳ disease (GD) of different sex. Clinical samples were collected from patients with GD with normal renal function to accurately validate eGFRCr and eGFRCysC levels and evaluate how hyperthyroidism affects renal function. Levels of eGFRCr and eGFRCysC showed clinical usefulness in successfully treated euthyroid patients with GD regardless of sex. The article includes detailed experimental methods and data used in our analysis. The data relates to the “Paradoxical effect of thyroid function on the estimated glomerular filtration rate by serum creatinine or standardized cystatin C in Japanese Graves’ disease patients” (Suzuki et al., 2015) [1]

Original Full Length ArticleSimilar frequency of paternal uniparental disomy involving chromosome 20q (patUPD20q) in Japanese and Caucasian patients affected by sporadic pseudohypoparathyroidism type Ib (sporPHP1B)☆

Highlights•Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance to parathyroid hormone.•In few sporPHP1B patients the disease is caused by paternal uniparental isodisomy involving chromosome 20q (patUPD20q).•We investigated 23 Japanese sporadic PHP1B cases to determine whether patUPD20q can be their cause of PHP1B.•PatUPD20q was confirmed for two patients.•Paternal duplication of the chromosomal region comprising the GNAS locus appears to be a relatively common cause of sporPHP1B.

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