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M Fukuzawa

Publications and source records attributed to M Fukuzawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tyrosine phosphorylation-independent nuclear translocation of a dictyostelium STAT in response to DIF signaling.

We describe a Dictyostelium STAT, Dd-STATc, which regulates the speed of early development and the timing of terminal differentiation. Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations. Developing Dictyostelium cells produce a chlorinated hexaphenone, DIF, which directs prestalk cell differentiation. Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells are exposed to DIF. Surprisingly, however, SH2 domain-phosphotyrosine interaction is not necessary for the DIF-induced nuclear translocation of Dd-STATc. In this respect, Dd-STATc activation resembles several recently described, noncanonical mammalian STAT signaling processes. We show instead that DIF mediates nuclear translocation via sequences located in the divergent, N-terminal half of the Dd-STATc molecule.

Amino Acid Sequence↗
PubMed2001

The inhibitor of apoptosis protein survivin is associated with high-risk behavior of neuroblastoma.

BACKGROUND/PURPOSE: Apoptotic factors inducing or preventing cell death may intrinsically govern the behavior of some tumors. Survivin is a recently described member of the inhibitor of apoptosis protein (IAP) family, that is expressed in a cell cycle-dependent manner and is found in tumors of unfavorable histology. This study examines the presence of several apoptotic factors, including survivin, in neuroblastoma (NB) tumors. Clues to survivin's function in NB are provided by examining its association with behavior and cell dynamics in tumors and cell lines. METHODS: Expression of a panel of apoptosis factors were quantified in 15 NB and related tumors before chemotherapy and in 3 NB cell lines (NB7, NB10, and NB16). Survivin and other apoptotic factors, as well N-myc amplification in primary tumors was correlated with recurrent disease and outcome. Proliferation rate, apoptosis assays, cell cycle analysis, and drug- or immune-mediated cell death were assessed in cell lines and evaluated in the context of differential survivin and apoptosis gene expression. RESULTS: All 7 tumors that went on to recur expressed survivin, whereas expression was absent in all 8 tumors that went into remission. N-myc was amplified in 4 (57.1%) of the 7 recurrent tumors. Of the 8 tumors that were cured, Fas was expressed in 3 (38%), TRAIL-R1 in 6 (75%) and tumor necrosis factor (TNF)-R1 in 8 (100%), whereas these pro-apoptotic receptors were present in only 1 (14%), 1 (14%), and 4 (57%) of the 7 tumors that went on to recur, respectively. Of the 3 cell lines, NB10 expressed the least survivin, displayed the lowest proliferation index, and had the fewest number of cells in the G2/M (mitotic) phase of the cell cycle. Furthermore, NB10 also was most sensitive to TNF-related apoptosis-inducing ligand (TRAIL) or etoposide-induced cell death. CONCLUSIONS: In primary NB tumors, survivin expression was associated with tumors of high risk and unfavorable prognosis, whereas pro-apoptotic receptor expression was more abundant in tumors of favorable prognosis. In this small series, survivin expression appeared to be more predictive of recurrent disease than N-myc amplification. In cell lines, survivin expression was cell cycle dependent, and its expression was associated with greater proliferation rates and greater resistance to drug- or immune-mediated cell death. Survivin expression may become a useful prognostic marker in NB and could be a potential target for the treatment of this tumor. J Pediatr Surg 36:1785-1791.

Apoptosis↗
PubMed2001

Laparoscopic extended cholecystectomy.

BACKGROUND: Inadvertent dissemination of latent gallbladder (GB) cancer has become a crucial issue with the widespread use of laparoscopic cholecystectomy as a standard operation for benign gallbladder diseases. METHODS: Laparoscopic extended cholecystectomy is a new technique we have developed for the resection of GB tumors with suspicion of malignancy. The procedure is safe and minimally invasive and prevents tumor dissemination. The GB is resected laparoscopically along with a 1-cm margin of the liver using LaparoSonic Coagulating Shears without any ligation or clipping. RESULTS: We applied this technique to a patient with a GB tumor in the fundus. The tumor was not exposed on the cut surface, and there were no postoperative complications. CONCLUSION: Laparoscopic extended cholecystectomy for GB tumors with suspicion of malignancy is a minimally invasive technique that may decrease the risk of tumor dissemination.

Cholecystectomy, Laparoscopic↗
PubMed2000

Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT protein.

Extracellular cAMP stimulates the rapid tyrosine phosphorylation and nuclear translocation of the DICTYOSTELIUM: STAT protein Dd-STATa. Here we show that it also induces serine phosphorylation by GskA, a homologue of glycogen synthase kinase-3 (GSK-3). Tyrosine phosphorylation occurs within 10 s of stimulation, whereas serine phosphorylation takes 5 min, matching the kinetics observed for the cAMP regulation of GskA. Phosphorylation by GskA enhances nuclear export of Dd-STATa. The phosphorylated region, however, is not itself a nuclear export signal and we identify a region elsewhere in the protein that mediates nuclear export. These results suggest a biphasic regulation of Dd-STATa, in which extracellular cAMP initially directs nuclear import and then, via GskA, promotes its subsequent export. It also raises the possibility of an analogous regulation of STAT nuclear export in higher eukaryotes.

Active Transport, Cell Nucleus↗
PubMed2000

Cloning and sequencing of the triacylglycerol lipase gene of Aspergillus oryzae and its expression in Escherichia coli.

Aspergillus oryzae produces at least three extracellular lipolytic enzymes, L1, L2 and L3 (cutinase, mono- and diacylglycerol lipase, and triacylglycerol lipase, respectively). We cloned the triacylglycerol lipase gene (provisionally designated tglA) by screening a genomic library using a PCR product obtained with two degenerate oligonucleotide primers corresponding to amino acid sequences of L3 as probes. Nucleotide sequencing of the genomic DNA and cDNA revealed that the L3 gene (tglA) has an open reading frame comprising 954 nucleotides, which contains three introns of 47, 83 and 62 bp. The deduced amino acid sequence of the tglA gene corresponds to 254 amino acid residues including a signal sequence of 30 amino acids and, in spite of the difference in substrate specificity, it is homologous to those of cutinases from fungi. Three residues presumed to form the catalytic triad, Ser, Asp and His, are conserved. The cloned cDNA of the tglA gene was expressed in Escherichia coli, and enzyme assaying and zymography revealed that the cloned cDNA encodes a functional triacylglycerol lipase.

Amino Acid Sequence↗
PubMed2000

Adjuvant-induced improvement of glucose intolerance in type 2 diabetic KK-Ay mice through interleukin-1 and tumor necrosis factor-alpha.

We reported that administration of complete Freund's adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls. The hypoglycemic effect of insulin was significantly, but partially, potentiated in the CFA-treated mice compared with the controls, suggesting that CFA stimulated insulin-mediated and non-insulin-mediated glucose disposal. Improvement in the GTT with CFA was partially transferable to nontreated mice by peritoneal exudative cells, but not spleen or lymph node cells. Pretreatment with anti-interleukin (IL)-1 alpha and -1 beta antibodies or anti-tumor necrosis factor (TNF)-alpha antibody significantly abrogated the improvement in the GTT with CFA. The results indicate that CFA-induced improvement in glucose intolerance in KK-Ay mice was mediated at least by IL-1 and TNF-alpha.

Animals↗
PubMed2000

Relation between gastroduodenal interdigestive migrating motor complex and postoperative gastrointestinal symptoms before and after cisapride therapy following distal gastrectomy for early gastric cancer.

A total of 30 patients (18 men, 12 women; 43-79 years, mean 58.9 years) 1.0 to 1.5 years (mean 1.25 years) after distal gastrectomy for early gastric cancer (Billorth I, D2 lymph node dissection, curability A) were divided into two groups based on the occurrence of interdigestive migrating motor complex (IMMC) phase III (pIII) from the duodenum and their postoperative gastrointestinal symptoms. They were compared before and after cisapride therapy (at an oral dose of 7.5 mg/day for 3 months). Results were as follows. Before cisapride therapy: (1) Patients in the IMMC-pIII-positive group (n = 20) had more appetite and ate more food with less decrease in body weight than those in the IMMC-pIII-negative group (n = 10); (2) patients in the IMMC-pIII-positive group clearly had fewer symptoms, such as early dumping (systemic) symptoms, symptoms of reflux esophagitis (e.g., heartburn, feeling of regurgitation, difficult swallowing), nausea, abdominal pain, diarrhea, abdominal distension, and borborygmus, than the IMMC-pIII-negative group. After cisapride therapy: eight patients (80%) in the IMMC-pIII-negative group became IMMC-pIII-positive, and their appetite and food consumption were obviously improved; body weight increased in six patients (60%), with alleviation of other abdominal symptoms and disappearance of the early dumping syndrome. These results showed a more satisfactory condition in regard to gastrointestinal symptoms in the IMMC-pIII-positive group than in the IMMC-pIII-negative group. It is concluded that cisapride therapy results in the occurrence of IMMC-pIII and subsequently alleviates various abdominal symptoms, contributing to the improved postoperative gastrointestinal condition of patients after gastrectomy.

Adult↗
PubMed2000

Determination of imbalance between MMP-2 and TIMP-2 in human neuroblastoma by reverse-transcription polymerase chain reaction and its correlation with tumor progression.

BACKGROUND/PURPOSE: The matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) have been implicated in tumor invasion and metastasis. Net matrix degradation and proteolysis depend on the critical local balance between MMPs/TIMP-2. We attempted to determine their expression balance and to evaluate its importance with tumor progression. METHODS: Expressions of MMP-2, MMP-9, and TIM P-2 mRNAs was quantified by reverse-transcription polymerase chain reaction (RT-PCR) in tumor tissues from 25 neuroblastoma patients. RESULTS: MMP-2, MMP-9, and TIMP-2 expression was observed in all the samples but with different trends. Increased expressions of MMP-2 mRNA was evident in advanced stages (Evans' stage III and IV; P = .02; unpaired ttest), and in patients who died of progressive disease (P = .0001). Whereas, the expressions of MMP-9 and TIMP-2 had no such significant association with clinical stages and prognosis. The ratio of MMP-2/TIMP-2 mRNAs was significantly higher in the advanced stages versus early stages (mean +/- SD = 1.66+/-0.65 and 1.11+/-0.34, respectively; P = .02) and in patients who died of progressive disease versus alive patients (mean = 2.13+/-0.78 and 1.21+/-0.36, respectively; P = .0006). CONCLUSIONS: Coexpression of MMPs and TIMP-2 in neuroblastoma indicates the need to evaluate their expression balance. Significantly higher expression of MMP-2 mRNA and increased ratio of MMP-2 and TIMP-2 mRNAs in advanced stages or patients who have died of progressive disease suggests an association between elevated MMP-2 expression and poor prognosis. To establish the role of enzyme to inhibitor mRNA ratio as a reliable predictor, cohort studies with significant number of cases may be carried out.

Base Sequence↗
PubMed2000

Modulation of tumor necrosis factor-alpha production with anti-hypertensive drugs.

It is well known that some anti-hypertensive drugs affect insulin sensitivity and that tumor necrosis factor-alpha (TNF-alpha) is a mediator of obesity-associated insulin resistance. In this study, we have investigated the effect of anti-hypertensive drugs, calcium (Ca) channel blockers (amlodipine, manidipine and nicardipine), an alpha(1)-blocker (doxazosin), a beta(1)-blocker (metoprolol), and a thiazide diuretic (hydrochlorothiazide), on lipopolysaccharide (LPS)-induced TNF-alpha production. TNF-alpha production, measured with a bioassay and an immunoassay, was evaluated both in vivo and in vitro, by utilizing mice and a human peripheral blood mononuclear cell culture, respectively. Nicardipine, or amlodipine, manidipine and doxazosin significantly inhibited TNF-alpha production in mice at doses more than one or ten times higher than those used clinically, respectively. On the other hand, metoprolol increased TNF-alpha production at doses of more than 10 times those used clinically, whereas hydrochlorothiazide did not alter production of the cytokine. The in vivo effects of these drugs were not necessary parallel to the in vitro effects. Because high doses of these drugs in mice correspond to clinical doses and effects in human, these actions may be related to beneficial and/or harmful effects of these drugs on TNF-alpha mediated diseases, including insulin resistance.

Adrenergic alpha-Antagonists↗
PubMed2000

Kaposi's varicelliform eruption of an elderly patient with multiple myeloma.

Kaposi's varicelliform eruption (KVE) is characterized by disseminated vesiculopustules and erosions due to a herpes virus infection superimposed on a preexisting dermatosis such as atopic dermatitis. However, the occurrence of KVE in patients with multiple myeloma seems to be very rare; to our knowledge, only one such case has been reported. This report documents a second case of KVE in a patient with multiple myeloma.

Aged↗
PubMed2000

Pancreatic ductal morphological pattern and dilatation in postoperative abdominal pain in patients with congenital choledochal cyst: an analysis of postoperative pancreatograms.

BACKGROUND: Postoperative abdominal pain associated with pancreatitis has been reported as a pancreas-associated complication after total biliary excision. The aim of the present study was to determine pancreatic ductal patterns in the head of the pancreas and evaluate pancreatic ductal dilatation in patients presenting with postoperative abdominal pain after radical biliary excision for congenital choledochal cyst. METHODS: Postoperative endoscopic retrograde pancreatography (ERP) was performed in a total of 38 patients (27 female and 11 male) with a history of postoperative abdominal pain or an increase in serum and urinary amylase on laboratory analysis. Pancreatic ductal configuration and ductal dilatation were determined. RESULTS: Pancreatic configurations included the usual type (n = 20), ansa pancreatica type (n = 11), loop type (n = 5), and divisum type (n = 2). Dilatation of the pancreatic duct was observed in 34 patients. The common channel was dilated in 29 patients. Mild postoperative pancreatitis occurred in 4 patients in the long term. Protein plugs were observed in the dilated pancreatic duct. CONCLUSIONS: Pancreatic ductal morphological pattern and ductal dilatation, possibly caused by long-standing stagnation of the pancreatic juice, may be associated with postoperative abdominal pain and pancreatitis in congenital choledochal cyst.

Abdominal Pain↗
PubMed2000

Deteriorating ischemic stroke in 4 clinical categories classified by the Oxfordshire Community Stroke Project.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the frequency, possible predictive factors, and prognosis of deteriorating ischemic stroke in 4 clinical categories according to the classification of the Oxfordshire Community Stroke Project (OCSP). METHODS: A total of 350 patients with first-ever ischemic stroke who presented within 24 hours of onset were enrolled. Based on the OCSP criteria, cerebral infarctions were divided into the following 4 clinical categories: total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar infarcts (LACI), and posterior circulation infarcts (POCI). Clinical deterioration was defined as a decrease of >/=1 points in the Canadian Neurological Scale (CNS) (in TACI, PACI, and LACI) or Rankin Scale (RS) (in POCI) during 7 days from the onset. In each clinical category, deteriorating (D) and nondeteriorating (ND) patients were compared in terms of their background characteristics, risk factors, vital signs, laboratory data, and cranial CT at the time of hospitalization. The acute-phase mortality and functional outcome were also compared. RESULTS: The subjects comprised 86 patients (24.6%) with TACI, 63 (18.0%) with PACI, 141 (40.3%) with LACI, and 60 (17.1%) with POCI. Overall, 90 patients (25.7%) deteriorated. The frequency was very high in TACI (41.9%), followed by LACI (26.2%) and POCI (21.7%), whereas it was very low in PACI (6. 3%). There were some clinical variables that differed significantly between D and ND groups. In the patients with TACI, early abnormalities of the cranial CT and significant stenoses in corresponding arteries were more frequent in the D than the ND group. In those with LACI, the CNS and hematocrit were lower in the D than the ND group. In those with POCI, cerebral atrophy was more severe and significant stenoses in vertebrobasilar arteries were more frequent in the D than ND group. The mortality of the D groups of patients with TACI and POCI exceeded 35%, and the functional outcome was worse in the D group than in the ND group of patients with TACI, LACI, and POCI. CONCLUSIONS: The frequency of deterioration in acute ischemic stroke significantly differed among the OCSP subgroups, and deterioration worsened the prognosis. There were some factors that could predict deterioration: early CT findings in TACI, large-artery atherosclerosis in TACI and POCI, and stroke severity in LACI. Further research to find sophisticated radiological and chemical markers appears to be needed.

Acute Disease↗
PubMed2000

Analysis of the promoter of the cudA gene reveals novel mechanisms of Dictyostelium cell type differentiation.

The cudA gene encodes a nuclear protein that is essential for normal multicellular development. At the slug stage cudA is expressed in the prespore cells and in a sub-region of the prestalk zone. We show that cap site distal promoter sequences direct cudA expression in prespore cells, while proximal sequences direct expression in the prestalk sub-region. The promoter domain that directs prespore-specific transcription consists of a positively acting region, that has the potential to direct expression in all cells within the slug, and a negatively acting region that prevents expression in the prestalk cells. Dd-STATa is the STAT protein that regulates commitment to stalk cell gene expression, where it is known to function as a transcriptional repressor. We show that Dd-STATa binds in vitro to the positively acting part of the prespore domain of the cudA promoter. However, Dd-STATa cannot be utilised for this purpose in vivo, because analysis of a Dd-STATa null mutant strain shows that Dd-STATa is not necessary for cudA transcription in prespore cells. In contrast, the part of the cudA promoter that directs prestalk-specific expression contains a binding site for Dd-STATa that is essential for its biological activity. Dd-STATa appears therefore to serve as a direct activator of cudA transcription in prestalk cells, while a protein with a DNA binding specificity highly related to that of Dd-STATa is utilised to activate cudA transcription in prespore cells.

Actins↗
PubMed2000

Isolation of sake yeast mutants producing a high level of ethyl caproate and/or isoamyl acetate.

In the case of sake, ethyl caproate and isoamyl acetate are considered to be closely associated with flavor. Various mutant yeast strains producing a higher level of flavor compounds (ethyl caproate and/or isoamyl acetate) than the parent strain were isolated by ethyl methane sulfonate treatment followed by global selection. Two of the mutants obtained also showed a high malate productivity. These mutants would be promising for practical sake fermentation.

Journal Article↗
PubMed2000

Left hepatic lobectomy for type IV-A choledochal cyst.

We report a case of a 37-year-old woman who was diagnosed with a type IV-A choledochal cyst with intrahepatic bile duct strictures. Because the stricture in the medial segment was located too far from the hilum for a hepaticojejunostomy we performed a left hepatic lobectomy. In this report we evaluate the therapeutic benefit of hepatectomy in a patient with a type IV-A choledochal cyst involving the intrahepatic bile ducts.

Adult↗
PubMed1999

Promoter analysis of the membrane protein gp64 gene of the cellular slime mold Polysphondylium pallidum.

We cloned a genomic fragment of the membrane protein gp64 gene of the cellular slime mold Polysphondylium pallidum by inverse PCR. Primer extension analysis identified a major transcription start site 65 bp upstream of the translation start codon. The promoter region of the gp64 gene contains sequences homologous to a TATA box at position -47 to -37 and to an initiator (Inr, PyPyCAPyPyPyPy) at position -3 to +5 from the transcription start site. Successively truncated segments of the promoter were tested for their ability to drive expression of the beta-galactosidase reporter gene in transformed cells; also the difference in activity between growth conditions was compared. The results indicated that there are two positive vegetative regulatory elements extending between -187 and -62 bp from the transcription start site of the gp64 promoter; also their activity was two to three times higher in the cells grown with bacteria in shaken suspension than in the cells grown in an axenic medium.

Animals↗