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K Dohi

Publications and source records attributed to K Dohi.

At least 145 records · Page 8Linked to original sources
PubMed1998

Production of adrenomedullin in macrophage cell line and peritoneal macrophage.

We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma (IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.

Adrenomedullin↗
PubMed1998

Early Breast Cancer Following Treatment of Myelodysplastic Syndrome: Report of a Case.

A 45-year-old woman was admitted to our hospital complaining of a mass in herleft breast. She had previously been diagnosed with myelodysplastic syndrome(MDS), a type of refractory anemia, based on bone marrow findings and chromosome analysis. She received a preoperative transfusion of fresh packed platelets and a recombinant human granulocyte colony-stimulating factor(rhG-CSF)injection. Left partial mastectomy and axillary lymph nodes dissection were performed to treat early breast cancer. Postoperatively, prophylactic radiotherapy of the residual breast and administration of medroxyprogesterone acetate(MPA)were performed because the tumor tissue was positive for progesterone receptors. She has remained clinically stable, with no evidence of recurrence, for more than three years to date. We report a rare case of breast cancer with MDS, treated with breast-conserving therapy. The strategy of pre- or postoperative platelet transfusion, rhG-CSFinjections, and hormonal therapy (MPA) appears to be suitable treatment for progesterone receptor(PgR)-positive breast cancer patients with MDS.

Journal Article↗
PubMed1998

Adrenomedullin production is correlated with differentiation in human leukemia cell lines and peripheral blood monocytes.

We demonstrated that adrenomedullin (AM) is produced and secreted from human leukemia cell lines (THP-1 and HL-60) as well as peripheral blood granulocytes, lymphocytes, monocytes and monocyte-derived macrophages. Immunoreactive AM accumulated in the culture media of THP-1 and HL-60 cells increased according to their differentiation into macrophage-like cells. Retinoic acid exerted synergistic effects on AM secretion from THP-1 and HL-60 cells when administered with tumor necrosis factor-alpha, lipopolysaccharide or 12-O-tetradecanoyl phorbol-13-acetate. AM was shown to increase the scavenger receptor activity on THP-1 cells. Thus, monocytes/macrophages should be recognized as sources of AM, and the secreted AM may modulate the function of macrophages.

Adrenomedullin↗
PubMed1998

Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B among Japanese subjects.

OBJECTIVE: To investigate HLA class II allele associations with autoantibody responses to Ro/SS-A and La/SS-B among Japanese subjects. METHODS: Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A and/or La/SS-B. RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 chain. HLA class II allele distributions did not differ among 3 anti-Ro/SS-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sjögren's syndrome, and women with no apparent symptoms of rheumatic disease. CONCLUSION: HLA class II allele distributions differ among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. Our findings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.

Adolescent↗
PubMed1998

Estimation of coronary flow reserve by intracoronary administration of nicorandil: comparison with intracoronary administration of papaverine.

We investigated the usefulness of the intracoronary administration of nicorandil (NIC) compared with that of papaverine (PAP) in the evaluation of coronary flow reserve (CFR) in 17 patients, including 10 patients with old myocardial infarction and 7 patients with angina pectoris. CFR was measured with a Doppler guidewire inserted into the distal site of the left anterior descending coronary artery during intracoronary administration of 10 mg PAP, and of 0.5 mg, 1.0 mg, 2.0 mg, and 3.0 mg NIC. We examined the changes in heart rate (HR), mean blood pressure (mBP), the total score of QTc interval on a 12-lead electrocardiogram (sigma QTc), and ST-T segment, before and after drug administration. CFR was significantly lower during administration of 0.5 mg (1.9 +/- 0.9) and 1.0 mg (2.2 +/- 0.9) NIC than during administration of PAP (2.6 +/- 1.1) (P < 0.01). There was no significant difference in the CFR during administration of 2.0 mg (2.6 +/- 1.0) or 3.0 mg (2.5 +/- 1.0) NIC and that observed during administration of PAP. The CFR during administration of PAP was significantly correlated with that during administration of 2.0 mg NIC (r2 = 0.72, P < 0.0001) and 3.0 mg NIC (r2 = 0.70, P < 0.0001). PAP, but not NIC, significantly altered the HR, mBP, and sigma QTc. Inverted T waves were observed in 14 patients, and elevation of the ST segment was observed in 4 patients during administration of PAP (including 1 patient with ventricular tachycardia). The administration of 0.5 mg to 2.0 mg NIC was not associated with ST-T segment changes, except in 1 patient, but inverted T waves were observed in 2 patients and depression of the ST segment was observed in 2 patients during administration of 3.0 mg NIC. Intracoronary administration of NIC is useful and safe for evaluating the CFR. The appropriate dose for measuring CFR is 2.0 mg nicorandil.

Angina Pectoris↗
PubMed1998

Magnetic resonance velocity mapping of transtricuspid velocity profiles in dilated cardiomyopathy.

To investigate the velocity profiles and jet sizes of transtricuspid inflow by magnetic resonance imaging (MRI), we examined seven dilated cardiomyopathy (DCM) patients (mean age 37 +/- 15 years) and 20 normal subjects (mean age 32 +/- 7 years). We used a Siemens Magnetom Impact Expert (1.0 T) together with a surface receiver coil. Electrocardiographic gating, triggered by the R wave, was performed. Cine gradient echo images were obtained in the short axis of the right ventricle. Velocity mapping of right ventricular inflow was obtained at peak early diastolic filling. Velocity profile curves across the tricuspid inflow were obtained at 1-cm intervals from the tricuspid ring up to 3 cm into the cavity. Maximum/mean velocities in both groups were 1.1 +/- 0.1 at the ring level, unchanged at 1 cm from the tricuspid ring, and thereafter increased to 1.4 +/- 0.3 at 2 cm and 1.5 +/- 0.3 at 3 cm as peak velocity fell. Jet cross-sectional area was 10.4 +/- 2.1 cm2 at the ring level, and was unchanged at the 3-cm level in the normal subjects. However, in patients with DCM it was smaller than that in normals, and decreased in proportion to the distance from the tricuspid ring. Thus, tricuspid inflow velocity showed a relatively flat profile at the tricuspid ring and tip levels, becoming more dispersed at 2 and 3 cm from the ring. The cross-sectional area of the right ventricular inflow jet in the DCM patients was small and decreased in proportion to the distance from the tricuspid ring, although it appeared to be relatively constant in normal subjects.

Adult↗
PubMed1998

Establishment of chimerism in donor liver with recipient-type bone marrow cells prior to liver transplantation produces marked suppression of allograft rejection in rats.

In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1-2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.

Animals↗
PubMed1998

Role of the bcl-2/bax pathway in hepatocyte apoptosis during acute rejection after rat liver transplantation.

It is well established that hepatocytes undergo apoptotic cell death in the course of rejection of liver grafts. The present study was designed to investigate the role of the bcl-2/bax pathway in liver allograft tissue. Orthotopic liver transplantation was performed in three groups of rats: group 1, a syngeneic combination (Lewis to Lewis), group 2, an allogeneic combination (ACI to Lewis), and group 3, an allogeneic combination (ACI to Lewis) treated with 15-deoxyspergualin. The number of apoptotic cells identified by the TUNEL method in the grafted liver reflected the severity of acute rejection. In group 1, both bcl-2 mRNA and bax mRNA were expressed in trace amounts. In group 2, bcl-2 mRNA was slightly expressed while the expression of bax mRNA rose steadily. In group 3, bcl-2 mRNA expression levels remained similar to group 1, while bax expression levels exceeded those in group 1, but were less than in group 2. Expression of bcl-2 mRNA was stationary in comparison with expression of bax mRNA. Significantly higher levels of bax mRNA were expressed from day 4 in group 2 than in group 1 (on postoperative days 4, 6, and 8, P < 0.05, group 2 vs group 1). We also investigated bax protein and results consistent with the mRNA analysis data were obtained. These findings suggest that apoptotic cell death in liver allograft rejection is regulated, at least in part, by bax.

Acute Disease↗
PubMed1998

Expression of bcl-2 homologue mRNAs in rat liver allograft: rejection-induced cell apoptosis is associated with upregulation of bax and bcl-xs expression.

Apoptosis is considered to play an important role in rejection of organ transplants, although the precise mechanism has not been elucidated. In this study, we screened for the expression of bcl-2 homologues (bcl-2, bax, bcl-xl, and bcl-xs) and Fas ligand (FasL) by RT-PCR method in grafts during acute rejection in rats following liver transplantation. Both bax and bcl-xs (inducers of apoptosis) mRNA levels increased steadily in the allografted group from postoperative day (POD) 2 to 8, while no remarkable changes of bcl-2 and bcl-xl expression (inhibitors of apoptosis) were recognized. Significant induction of FasL gene expression was observed in the allografted group on POD 4 and expression gradually decreased thereafter, although minimal FasL mRNA expression was seen in isografts. Our results indicated, for the first time, that rejection-induced cell apoptosis is closely associated with upregulation of bax and bcl-xs expression besides FasL, but not with down-regulation of bcl-xl.

Animals↗
PubMed1998

TNF-alpha and heat-shock protein gene expression in ischemic-injured liver from fasted and non-fasted rats. Role of donor fasting in the prevention of reperfusion injury following liver transplantation.

We have previously shown that livers from long-term-fasted rats acquire tolerance to warm ischemic injury following transplantation, despite the fact that fasting depletes glycogen and ATP from the liver. The precise mechanism of the protective effect induced by donor fasting, however, is still a matter of controversy. In this experiment we determined heat-shock protein (GRP78) mRNA expression in livers during long-term fasting and TNF-alpha mRNA expression in transplanted livers exposed to warm ischemia. We also measured the concentration of TNF-alpha by ELISA in the ascitic fluid of fed and fasted rats injected intraperitoneally with zymosan to investigate why livers from fasted rats tolerate ischemic injury better. There seemed to be a positive correlation between GRP78 mRNA expression and survival. TNF-alpha secretion into the ascitic fluid of fasted rats was markedly suppressed, and fasting donor animals induced cytoprotective substances, such as GRP78, in the liver. These factors may contribute to the tolerance to ischemic injury produced by donor fasting.

Animals↗
PubMed1998

Effect of FTY720 on immunoregulation in concordant xenotransplantation.

The present study was designed to analyze the immunosuppressive activity of FTY720 in concordant xenotransplantation. When T and B lymphocytes of human peripheral blood were incubated with FTY720, the number of viable cells decreased in a dose-dependent manner at doses higher than 4 x 10(-5) M. DNA fragmentation was observed at doses higher than 1 x 10(-5) M in T cell-rich fractions and at doses higher than 4 x 10(-5) M in B cell-rich fractions. These data demonstrate that FTY720 is cytotoxic to B lymphocytes as well as T lymphocytes and apoptosis may play an important role in this cytotoxicity. Golden Syrian hamsters were the donors and Lewis rats the recipients of skin grafts. The recipients were divided into the following four groups: (1) untreated recipients, (2) FTY720 (5 mg/kg per day) was administered orally for 8 days (days-1-6), (3) FK506 (1 mg/kg per day) was injected i.m. for 7 days (days 0-6), and (4) FK506 (1 mg/kg per day) was injected i.m. for 7 days (days 0-6) and FTY720 (5 mg/kg per day) was administered orally for 8 days (days-1-6). The mean graft survival times in groups 1-4 were 9.7 +/- 0.52 days (n = 6), 12.0 +/- 0.71 days (n = 6), 13.2 +/- 1.6 days (n = 6), and 37.7 +/- 4.3 days (n = 6), respectively. There was a significant difference in the mean survival time between groups one and four. Combined therapy with FTY720 and FK506 is a useful tool for immunoregulation in xenotransplantation.

Animals↗
PubMed1998

Isolated caudate lobectomy by anterior approach for hepatocellular carcinoma originating in the paracaval portion of the caudate lobe.

We aimed to assess isolated caudate lobectomy by the anterior approach for the treatment of large hepatocellular carcinomas originating in the paracaval portion of the caudate lobe. The surgical procedures consisted of ligation and dissection of the caudate branch of the portal vein and short hepatic veins from the right side of the hepatic hilum; liver resection cranially from the right side of the process portion; ligation and dissection of the short hepatic veins from the left side; hepatic resection between the lateral segment and Spiegel lobe; and, finally, dissection of the liver at the right of the Cantlie line, reaching the tumor in the paracaval portion of the caudate lobe. The important point in this procedure was the appropriate management of the short hepatic veins, the branches of the hepatic vein, and the glisson's vessels of the paracaval portion. The operative times for the three patients reported here were 430, 355, and 575 min, with blood loss of 1100, 1180, and 2000 ml, respectively. The duration of the operation was short and blood loss was minimal; severe complications were not observed. Complete recovery of liver function after this surgery tended to be slow. Early recurrence was observed during long-term follow-up. This procedure is considered to be a safe method, with optimal surgical vision for caudate lobe tumors of a relatively large size. However, adjuvant therapy to prevent recurrence is required.

Aged↗
PubMed1998

Malignant mesothelioma originating in the hepatic falciform ligament: report of a case.

We report herein what to our knowledge is the first documented case of malignant mesothelioma arising from the falciform ligament. A 65-year-old woman was admitted to our department for the evaluation of an epigastric mass. An abdominal computed tomography scan, magnetic resonance imaging, and celiac angiogram showed a tumor originating in the falciform ligament. The tumor was subsequently resected, and pathological examination confirmed a diagnosis of malignant mesothelioma originating in the falciform ligament. A metastatic liver tumor was detected 3 years after this operation and a partial liver resection was performed. She is currently off therapy, and no clinical or radiologic evidence of disease has been found for 1 year since her second operation.

Aged↗
PubMed1998

Pancreatic duct obstruction is an aggravating factor in the canine model of chronic alcoholic pancreatitis.

BACKGROUND & AIMS: Chronic alcoholic pancreatitis occurs in only a limited number of heavy drinkers. Other factors than alcohol are necessary for the occurrence of chronic alcoholic pancreatitis. The aim of this study was to examine whether pancreatic duct obstruction resulted in increased alcohol-induced parenchymal cell damage. METHODS: Four groups of adult mongrel dogs were used. In group A, 2. 0 g . kg-1 . day-1 of ethanol was administered via a gastric cannula. In group O, after ligation of the minor pancreatic duct, a polyethylene tube was inserted transduodenally into the major duct. In group AO, the protocols used in groups A and O were combined. Laparotomy was repeated after 3 months in each group. RESULTS: Three of the 9 dogs in group AO had pancreatic calculi in the main pancreatic duct. Moderate interlobular fibrosis, parenchymal cell loss, and inflammatory cell infiltration resembling human chronic alcoholic pancreatitis were observed in group AO. Little change was observed in groups A and O. Exocrine function assessed by secretin test in group AO was significantly reduced. Total protein, hexosamine, and calcium contents of the pancreatic juice in group AO were significantly increased. CONCLUSIONS: Pancreatic duct obstruction is an aggravating factor in chronic alcoholic pancreatitis.

Acute Disease↗
PubMed1998

Does increased QT dispersion in the acute phase of anterior myocardial infarction predict recovery of left ventricular wall motion?

QT dispersion has been recognized as an undesirable marker because of its association with arrhythmogenicity in patients with myocardial infarction, but the relation between QT interval dispersion and wall motion abnormalities has not been clarified. After the introduction of reperfusion therapy, it was recognized that T waves were inverted twice in the course of myocardial infarction. An investigation was made of the clinical significance of QT dispersion in relation to the presence of inverted T waves and left ventricular wall motion abnormalities in 34 patients (mean age, 59 years) with acute anterior myocardial infarction who underwent successful reperfusion therapy. The amplitude of the deepest inverted T waves occurring within the first 3 days (T1) and after 3 days (T2) of myocardial infarction were measured in electrocardiographic (ECG) lead V3. On the ECGs on which T1 and T2 were recorded, QT dispersion was calculated (QTd1, QTd2), and T1 and T2 were correlated with QTd1 (r = .65) and QTd2 (r = .47), respectively. The difference between the extent of asynergy in the acute phase and the chronic phase, which was evaluated by the centerline method, was correlated with T1 (r = .63) and QTd1 (r = .67). Patients with a QTd1 of 0.1 second or longer showed a greater change in the extent of asynergy (23.4 +/- 13.1% vs 4.9 +/- 9.8%, P < .01) and less asynergy in the chronic phase (19.9 +/- 15.6% vs 46.5 +/- 14.0%, P < .01) than patients with a QTd1 of less than 0.1 second. Thus, QT dispersion in the acute phase of anterior myocardial infarction indicates recovery of left ventricular wall motion. Prolongation of the local action potential duration of the myocardium that recovers from severe ischemia may be a contributor to the increased QT dispersion that results in inversion of T waves in the acute phase of myocardial infarction.

Electrocardiography↗