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K Kawanishi

Publications and source records attributed to K Kawanishi.

At least 19 recordsLinked to original sources
PubMed1999

Cytoplasmic beta-catenin in esophageal cancers.

beta-Catenin has 2 distinct roles in E-cadherin-mediated cell adhesion and carcinogenesis through APC gene mutation. One occurs at cell-adhesion sites, where cadherins become linked to the actin-based cytoskeleton. The others occur in the cytoplasm and nuclei and are thought to regulate cell transformation. We studied these different beta-catenins and evaluated their significance in carcinogenesis. Fresh surgical specimens were obtained from 22 patients with squamous-cell carcinoma of the esophagus. beta-Catenin in the free soluble fraction and the insoluble fraction was immunoblotted separately. At the same time, its localization was observed by immuno-histochemical techniques. In the normal esophageal epithelium, 91% of beta-catenin was detected in the insoluble fraction and beta-catenin staining occurred at the cell membrane, in co-existence with E-cadherin. In cancerous tissues, the amount of soluble beta-catenin was significantly (about 4-fold) higher than in normal tissues. Also, in cancerous tissues with higher amounts of soluble beta-catenin, immuno-histochemical techniques revealed the presence of beta-catenin in the cytoplasm and nuclei, as well as in the cell membrane. However, in samples with lower amounts of beta-catenin, expression was found only at the cell boundaries. The amount of soluble beta-catenin was not associated with the clinico-pathological grading of the tumors. Our results show that the accumulation of free soluble beta-catenin in the cytoplasm and nuclei frequently occurs during carcinogenesis of the squamous epithelium of the esophagus.

Animals↗
PubMed1998

Angoline and chelerythrine, benzophenanthridine alkaloids that do not inhibit protein kinase C.

Starting with an extract derived from the stem of Macleaya cordata (Papaveraceae) that was active in the process of inhibiting phorbol 12,13-dibutyrate binding to partially purified protein kinase C (PKC), the benzophenanthridine alkaloid angoline was isolated and identified. This discovery appeared in context, as a related benzophenanthridine alkaloid, chelerythrine, has been reported to mediate a variety of biological activities, including potent and selective inhibition of protein kinase C (PKC). However, in our studies, angoline was not observed to function as a potent inhibitor of PKC. Moreover, we were unable to confirm the reported inhibitory activity of chelerythrine. In a comprehensive series of studies performed with various PKC isozymes derived from a variety of mammalian species, neither chelerythrine nor angoline inhibited activity with high potency. To the contrary, chelerythrine stimulated PKC activity in the cytosolic fractions of rat and mouse brain in concentrations up to 100 microM. In addition, chelerythrine and angoline did not inhibit [3H]phorbol 12,13-dibutyrate binding to the regulatory domain of PKC at concentrations up to 40 microg/ml, and no significant alteration of PKC-alpha, -beta, or -gamma translocation was observed with human leukemia (HL-60) cells in culture. Further, chelerythrine did not inhibit 12-O-tetradecanoylphorbol 13-acetate-induced ornithine decarboxylase activity with cultured mouse 308 cells, but angoline was active in this capacity with an IC50 value of 1.0 microg/ml. A relatively large number of biological responses have been reported in studies conducted with chelerythrine, and alteration of PKC activity has been considered as a potential mechanism of action. In light of the current report, mechanisms independent of PKC inhibition should be considered as responsible for these effects.

Alkaloids↗
PubMed1998

A new cytokine-dependent monoblastic cell line with t(9;11)(p22;q23) differentiates to macrophages with macrophage colony-stimulating factor (M-CSF) and to osteoclast-like cells with M-CSF and interleukin-4.

Monocytes/macrophages exert a series of important functions in vivo. To facilitate detailed investigation of their functional capacity and the mechanism leading to their differentiation, several cell lines have been established from primary material. We present here a new human monoblastic cell line, designated UG3. UG3 cells are characterized by the following features. (1) UG3 cells harbor the t(9;11)(p22;q23) translocation that results in fusion of the MLL and the AF9 genes and produce the corresponding AF9-MLL and MLL-AF9 fusion transcripts. (2) UG3 cells rely on the presence of exogenous growth factors for viability and proliferation, such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), or macrophage colony-stimulating factor (M-CSF). (3) When cultured in the presence of G-CSF, UG3 cells differentiate along the granulocytic lineage, as evidenced by segmentation of nuclei and positive staining for neutrophilic alkaline phosphatase and peroxidase. (4) When cultured in the presence of GM-CSF or M-CSF, UG3 cells differentiate into mature macrophages while preserving surface expression of CD14 and CD68 and also start to release cytokines into cell-culture supernatants. Under these culture conditions, UG3 cells also take up acetylated LDL. (5) When cultured in the presence of M-CSF and IL-4, UG3 cells differentiate into osteoclast-like multinucleated giant cells capable of bone resorption and display tartrate-resistant acid phosphatase (TRAP) activity. UG3 cells thus provide features to qualify them as a useful model to further investigate the mechanism underlying these processes and also to further elucidate the functional role of mature monocytes/macrophages or osteoclasts.

Adult↗
PubMed1998

Edg-2/Vzg-1 couples to the yeast pheromone response pathway selectively in response to lysophosphatidic acid.

We have functionally expressed the human cDNA encoding the putative lysophosphatidic acid (LPA) receptor Edg-2 (Vzg-1) in Saccharomyces cerevisiae in an attempt to determine the agonist specificity of this G-protein-coupled receptor. LPA activated the pheromone response pathway in S. cerevisiae expressing Edg-2 in a time- and dose-dependent manner as determined by induction of a pheromone-responsive FUS1::lacZ reporter gene. LPA-mediated activation of the pheromone response pathway was dependent on mutational inactivation of the SST2 gene, the GTPase-activating protein for the yeast G alpha protein (the GPA1 gene product). This indicates that, in sst2 delta yeast cells, Edg-2 can efficiently couple to the yeast heterotrimeric G-protein in response to LPA and activate the yeast mitogen-activated protein kinase pathway. The Edg-2 receptor showed a high degree of specificity for LPA; other lyso-glycerophospholipids, sphingosine 1-phosphate, and diacyl-glycerophospholipids did not activate FUS1::lacZ. LPA analogs including a cyclic phosphoester form and ether-linked forms of LPA activated FUS1::lacZ, although fatty acid chains of 6 and 10 carbons did not activate FUS1::lacZ, suggesting a role for the side chain in ligand binding or receptor activation. These results indicate that Edg-2 encodes a highly specific LPA receptor.

Dose-Response Relationship, Drug↗
PubMed1998

Both positive and negative portal venous and hepatic arterial glucose gradients stimulate hepatic glucose uptake after the same amount of glucose is infused into the splanchnic bed in conscious dogs.

We studied the effects of both positive and negative portal venous and hepatic arterial glucose gradients on hepatic glucose uptake after the same amount of glucose was administered into the portal vein and/or hepatic artery. Studies were performed on eight unrestrained conscious dogs with catheters in the portal vein, hepatic vein, gastroduodenal artery, superior mesenteric vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Glucose was infused as follows: protocol 1, 55.6 micromol/kg/min into the portal vein for the first 90 minutes; protocol 2, 27.8 micromol/kg/min into both the portal vein and hepatic artery for the next 90 minutes; and protocol 3, 55.6 micromol/kg/min into the hepatic artery for the last 90 minutes. The portal venous and hepatic arterial plasma glucose gradient was 2.1+/-0.3, -3.0+/-0.5, and -7.1+/-0.6 mmol/L, the rate of hepatic glucose uptake divided by the administered glucose load was 46%+/-11%, 42%+/-10%, and 57%+/-8%, net hepatic glucose uptake was 25.4+/-5.9, 23.5+/-5.6, and 31.6+/-4.6 micromol/kg/min; and the fractional hepatic extraction of glucose was 10.7%+/-2.2%, 11.6%+/-2.5%, and 15.0%+/-2.1%, respectively (mean+/-SEM of three points at 60, 75, and 90 minutes in each protocol). The rate of hepatic glucose uptake divided by the administered glucose load, net hepatic glucose uptake, and fractional hepatic extraction of glucose did not change significantly despite the various portal venous and hepatic arterial glucose gradients. We also studied the effect of the same amount of intraportal glucose infusion for 240 minutes on net hepatic glucose uptake. From 60 to 240 minutes, net hepatic glucose uptake did not change significantly. In conclusion, the liver took up a large amount of glucose administered into the portal vein and/or hepatic artery, regardless of positive or negative portal venous and hepatic arterial glucose gradients. Augmentation of hepatic glucose uptake is not dependent on the signal of the positive or negative portal venous and hepatic arterial glucose gradient.

Animals↗
PubMed1998

A novel mature B-cell line (DOBIL-6) producing both parathyroid hormone-related protein and interleukin-6 from a myeloma patient presenting with hypercalcaemia.

A novel human EBV-negative B-cell line, designated DOBIL-6, was established from a patient with non-secretary myeloma. The DOBIL-6 cell has cytoplasmic gamma protein and expresses CD19, 20, 38, 45RO, VLA-4 and PCA-1 antigens, but lacks CD10, 45RA and VLA5 antigens. Chromosome analysis showed that DOBIL-6 cells had many complex structural abnormalities, including t(11;4) (q13;q32), which were consistent with that of the fresh tumour cells. Interestingly, abundant interleukin-6 (IL-6) and parathyroid hormone-related protein (PTHrP) accumulated in the culture supernatant of DOBIL-6 cells. Hypercalcaemia and splenomegaly associated with plasma cell proliferations which resulted in the expansion of the light zones in the follicles were observed in DOBIL-6 transplanted nude mice. RT-PCR analysis detected mRNA for PTHrP, and IL-6 as well as its receptor (GP80) in DOBIL-6 cells. Treatment of the DOBIL-6 cells with neutralizing anti-IL-6 antibody inhibited their growth in a dose-dependent manner, whereas the addition of exogenous IL-6 stimulated it in serum-depleted conditions. These findings suggest that both IL-6 and PTHrP are produced in DOBIL-6 cells, and that IL-6 promotes its growth by an autocrine mechanism. Since IL-6 is known to stimulate not only the growth of B-cell neoplasms but also osteoclastic bone resorption by cooperating with PTHrP, this simultaneous production of IL-6 and PTHrP might be synergistically linked and play a role in the development of hypercalcaemia of the patient. The DOBIL-6 cell is a useful tool to clarify the mechanism of hypercalcaemia associated with mature B-cell neoplasms.

Aged↗
PubMed1998

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia.

A 31-year-old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon-alpha since February 1995. After 16 months, he complained of low-grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X-ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Adult↗
PubMed1998

Automated fluorimetric determination of cellular cholesterol.

We developed a completely automated fluorimetric method for the determination of cellular cholesterol, consisting of enzymatic hydrolysis of cholesteryl ester to free cholesterol and enzymatic oxidation of free cholesterol in the presence of an indicator substrate to produce a fluorescent product. For control preparations of monocytes, the mean detection limit was 2.57 mumol/5 x 10(5) cells and the mean within-batch coefficients of variation were 9.30, 6.00 and 3.73% at mean cholesterol concentrations of 1.94, 9.05 and 12.49 mumol/5 x 10(5) cells, respectively. The results correlated well with those obtained by gas-liquid chromatography.

Adult↗
PubMed1998

[An elderly patient with an insulinoma who had prolonged dementia-like symptoms].

A 77-year-old woman had suffered from memory disturbance and disorientation for two years before she was admitted to the hospital because of confusion. Her score on the Hasegawa dementia scale revised (HDS-R) was 12 points at the time of the first medical examination. No other abnormalities could be found except for a blood glucose concentration of 34 mg/ dl. A Magnetic Resonance Image (MRI) of the brain showed some small lacunae on both sides in the frontal white matter and basal ganglia. After hospitalization, glucose was administered and the blood glucose concentration increased, but the dementia-like symptoms did not resolve. She was discharged because the symptoms were too difficult to control in the general hospital. Although dementia-like symptoms were present even after discharge, they did not necessarily appear during fasting. Six months later she was rehospitalized. The insulin-blood sugar ratio was at least 0.3 and abdominal echogram showed a 1-cm tumor at the tail of pancreas. The pancreas tail was removed and the tumor cells were reacted with anti-insulin-antibodies. One month after the operation, the dementia-like symptoms had resolved. The HDS-R score was improved to 27 points (normal range) 40 days after the operation. The amount of the slow waves in the electroencephalogram decreased 5 months after the operation. The dementia-like symptoms observed in this case could be regarded as the Durchgangssyndrom of Wieck. This syndrome is observed transiently at the time of recovery of deterioration of disturbances of consciousness. But it is treatable. This patient was an interesting case that showed Durchgangssyndrom mimiking dementia associated with insulinoma.

Aged↗
PubMed1998

[Lactate metabolism and lactic acidosis].

Lactate can be viewed as a metabolic dead end in that it can only be produced or utilized via pyruvate. Lactate production is determined primarily by pyruvate concentration and to a lesser extend by the redox state. Increased lactate production may result from tissue hypoxia, alkalosis, catecholamine and alanine transamination to pyruvate. Hyperlactatemia is observed in many pathological conditions. Current diagnostic criteria for lactic acidosis are a pH less than 7.35 and lactate concentration greater than 5 to 6 mmol/l. In our study series, malignancy was the most common underlying disease accompanied by lactic acidosis. Organ failure, cardiovascular disease and diabetes mellitus were also common. The prognosis of patients with these diseases were grave. In cases of lactic acidosis associated with diabetes mellitus, alcoholic liver disease, rhabdomyolysis and diabetic comas were noticeable as complications. Alcohol abuse was the most common cause of lactic acidosis associated with diabetes mellitus. In these cases, laboratory data showed prominent hyperlactatemia, hyperglycemia and acidemia and elevated anion gap. The mortality rate in these cases was 36% and higher in cases with organ failure. Treatment of lactic acidosis consists of alkalization by sodium bicarbonate with carbicarb, insulin-glucose-infusion, dichloroacetate therapy, tham administration, bicarbonate-buffered peritoneal dialysis and high bicarbonate-containing dialysis.

Acidosis, Lactic↗
PubMed1997

Investigation of nosocomial infection caused by arbekacin-resistant, methicillin-resistant Staphylococcus aureus.

An outbreak of coagulase VII-producing, arbekacin (ABK)-resistant, methicillin-resistant Staphylococcus aureus (MRSA) occurred between September 1994 and December 1995, involving five different wards. Twenty-one patients developed skin, wound, drainage, or respiratory tract colonization with coagulase VII-producing, (ABK)-resistant MRSA. Phenotypic characteristics (production of enterotoxin and TSST-1, antimicrobial susceptibility) and molecular-typing procedure (plasmid DNA profile, pulsed-field gel electrophoresis [PFGE] and arbitrarily primed polymerase chain reaction [AP-PCR] of chromosomal DNA) in isolated strains were compared. Plasmid analysis identified four different profiles and 19 of 22 strains recovered had identical patterns. PFGE of chromosomal DNA identified three different subtypes and 18 (81.8%) isolates shared the same subtype. AP-PCR also demonstrated that most strains had the same phenotypic characteristics. Although traditional epidemiological methods; for example, coagulase typing, plays a central role in hospital infection control, combination of plasmid DNA profile, AP-PCR, and PFGE may prove to be a particularly informative means of tracking the nosocomial spread of MRSA.

Adult↗
PubMed1997

GM-CSF- and IL-3-dependent CD34 expressing myeloid cell line (SAS-1) established from CD7 and CD34 expressing acute myeloblastic leukemic cells.

A novel factor-dependent human myeloid leukemia cell line (SAS-1) was established from a 69-year-old Japanese male suffering from CD7 and CD34 expressing acute myeloblastic leukemia (AML M2 in FAB classification). Morphological and cytochemical staining showed that SAS-1 cells were round with basophilic cytoplasm which is positive for peroxidase. Analysis of surface markers revealed that SAS-1 cells were myeloblasts derived from an immature progenitor origin, which express CD34. The consensus karyotype of the cell line was 41 XY 5q-, -7, 11p-, 12p+, -13, -14, -16, -17, -19, -22, with two markers. The proliferation of SAS-1 cells was dependent on the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and GM-CSF- and IL-3-induced proliferation was dose dependent. Neither, stem cell factor (SCF) nor granulocyte colony-stimulating factor (G-CSF) alone supported the growth of SAS-1 cells, but supported their viability for more than 4 days and arrested them in the G0/G1 phase. SCF also enhanced GM-CSF- or IL-3-induced growth, but other cytokines did not have this synergistic effect. Clonogenic assays revealed that SAS-1 cells formed 36.0 +/- 5.7 or 41.5 +/- 0.7 colonies/1000 cells in the presence of GM-CSF or IL-3, respectively. SCF also increased the number of colonies formed by GM-CSF or IL-3 treatment, while SAS-1 cells did not form colonies in the presence of SCF alone. SAS-1 cells may prove to be a useful tool for studying the regulation of the cell cycle, myeloid proliferation, and differentiation.

Aged↗
PubMed1997

Malignant melanoma of the uterine cervix: a case report.

We present case of a 57-year-old Japanese woman a 9 cm-size primary malignant melanoma of the uterine cervix. MRI demonstrated a low-signal T1-weighted spin echo image and hyperperfusion indicated by Gd-DTPA enhancement. The sequence analysis of the MTS1/CDK4I gene revealed no deletion or mutation. The results of cytological, pathological, and electron microscopy tests are also presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Effect of continuous intravenous injection of interleukin-6 and pretreatment with cyclooxygenase inhibitor on brain c-fos expression in the rat.

The aim of the present study was to assess potential brain sites of stimulation by peripheral interleukin (IL)-6 of the hypothalamo-pituitary-adrenal (HPA) axis in the rat, using c-fos protein as a marker of cellular activation. Involvement of prostaglandins in IL-6-induced ACTH secretion and c-fos expression was also investigated. IL-6 was infused continuously (40 ng/min) for 90 min to conscious male rats. Blood samples were taken before the infusion and at 30 and 90 min for measurement of plasma ACTH. Expression of c-fos in the brain was examined by immunohistochemistry. Administration of IL-6 significantly elevated plasma ACTH levels at 30 min (495 +/- 105 vs. 117 +/- 17 pg/ml in controls, p < 0.05). Elevated levels were still present at 90 min (596 +/- 139 vs. 113 +/- 20 pg/ml in controls, p < 0.05). Infusion of IL-6 (3.6 micrograms/rat) markedly triggered c-fos expression in hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), as well as in the central amygdaloid nucleus (CeA), the nucleus tractus solitarius and the locus coeruleus. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg, i.v.) suppressed the ACTH response induced by IL-6. The number of IL-6-induced immunoreactive cells in the PVN was significantly reduced by indomethacin pretreatment (p < 0.01), but the number of IL-6-induced c-fos-positive cells in the SON and CeA remained unchanged. These findings suggest that circulating IL-6 may exert central actions by acting directly or indirectly on brain neurons. In addition, the ability of IL-6 to activate the HPA axis may depend upon the release of prostaglandins, probably in the brain.

Adrenocorticotropic Hormone↗
PubMed1997

The effect of somatostatin analogue on glucose homeostasis in conscious dogs.

Our aim was to clarify the effect of a somatostatin analogue (octreotide) on glucose flux in conscious dogs. We monitored the effects with catheters in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery before and after oral glucose administration. A significant increase of portal vein plasma flow after oral glucose was completely suppressed by both 4 and 1 micrograms/kg octreotide. All doses of octreotide (4, 1 and 0.1 microgram/kg) suppressed the glucose-induced increment of arterial glucose by dose response. Only 4 micrograms/kg of octreotide slightly but significantly suppressed hepatic glucose output. Marked suppression and delayed glucose absorption by the intestine was observed after 4 micrograms/kg of octreotide. One and 0.1 microgram/kg octreotide also suppressed glucose absorption without delayed absorption. Total amounts of absorbed glucose during 3h after oral glucose were 24 +/- 11% with 4 micrograms/kg of octreotide, 37 +/- 16% with 1 microgram/kg of octreotide, and 48 +/- 8% with 0.1 microgram/ kg of octreotide, all of which were significantly less than that of the control (73 +/- 8%). Using 4 micrograms/kg of octreotide treatment, the liver took up only 5 +/- 4% of the absorbed glucose, while the liver took up 35 +/- 6% and 43 +/- 9% of the absorbed glucose with 1 and 0.1 microgram/kg of octreotide. These latter values were similar to that of the control value of 34 +/- 4%. In conclusion, we found that octreotide administered before oral glucose had a remarkable stabilizing effect on postprandial glycemic surges. Both the direct inhibitory effect of octreotide on portal vein plasma flow and impaired glucose absorption would contribute to this decreased postprandial hyperglycemia, while its suppressive effect on other hormones, such as insulin and glucagon, did not seem to influence the reduction of hyperglycemia.

Animals↗
PubMed1997

[Lactic acidosis].

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Acidosis, Lactic↗
PubMed1996

Human herpesvirus 6 induces IL-8 gene expression in human hepatoma cell line, Hep G2.

The infectivity of human herpesvirus 6 (HHV-6) in a human hepatoma cell line, Hep G2 cells, and the effect of HHV-6 on production of inflammatory cytokines in these cells were examined to analyze pathogenesis of HHV-6 in the liver. We demonstrated that Hep G2 cells were susceptible to infection with HHV-6, and produced infectious virus. Moreover, infection of Hep G2 cells by HHV-6 induced the expression of IL-8 mRNA, but not IL-1 beta. The effect on induction of IL-8 gene expression was observed only in Hep G2 cells infected with infectious virus, whereas both heat-inactivated HHV-6 and UV-irradiated HHV-6 did not change the IL-8 mRNA level in these cells. These data suggest that HHV-6 may induce the cytokine-mediated inflammatory response by infecting liver cells, which could result in liver dysfunction in vivo.

Antigens, Viral↗