Characterization of a newly established human gallbladder carcinoma cell line.
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Adenocarcinoma↗
Biomedical subjects
Y Niho
Publications and source records attributed to Y Niho.
IL-10 inhibits prostaglandin E2 production by lipopolysaccharide-stimulated monocytes.
Since IL-10 has recently been shown to exhibit pleiotropic effects on human monocytes, it was of interest to determine the effect of this cytokine on prostaglandin E2 (PGE2) production by monocytes. Recombinant IL-10 (rIL-10) did not significantly affect PGE2 production by lipopolysaccharide (LPS)-unstimulated monocytes, but efficiently inhibited PGE2 production by LPS-stimulated monocytes. The inhibition by rIL-10 was achieved in a dose-dependent manner. Recombinant IL-4 also inhibited PGE2 production at the same degree as rIL-10. Viral IL-10 inhibited PGE2 production by monocytes in a similar fashion as did human rIL-10. Endogenously produced IL-10 was also shown to inhibit PGE2 production by LPS-stimulated monocytes. Kinetic studies showed that the inhibition by rIL-10 on PGE2 production was observed at least 3 h after LPS stimulation. Taken together, these results indicate that IL-10 may play an important role in modulating immunological responses via down-regulation of PGE2 production by monocytes.
Cells, Cultured↗
Imaging study on the mode of development and changes in avascular necrosis of the femoral head in systemic lupus erythematosus: long-term observations.
To find out when and how avascular necrosis of the femoral head (ANFH) develops in patients with SLE who are receiving corticosteroids, we carried out a 3-yr prospective study using imaging methods. Twenty-three patients with SLE who were free of hip pain and radiographically negative were enrolled in the study. Initially, abnormal findings characteristic of ANFH were detected in eight (35%) and six (26%) patients on MRI and radionuclide uptake bone scanning, respectively. During a 3-yr observation period abnormalities on MRI, bone scanning and radiography were found in four, five and four patients, respectively and three patients developed hip pain. Analyses of imaging changes demonstrated that only a small proportion of patients (2/8, 25%) who initially showed abnormal MRI progressed to be radiographically positive for ANFH over the 3 years. High doses of corticosteroids over the 3-yr period were to be responsible for the emergence of change in MRI abnormalities. It is also suggested that abnormal MRI findings tend to develop either within a relatively short interval after the start of corticosteroid treatment or are associated with the exacerbation of SLE.
Adolescent↗
Characterisation of the external surfaces of Pseudomonas aeruginosa isolated from human blood and respiratory tract.
The surface structures of the cell envelopes of 16 clinical isolates of Pseudomonas aeruginosa were examined by electronmicroscopy with the new fixation technique of freeze-substitution. Two types of structures were observed among the organisms. In one group of strains, mostly isolated from blood, a dense fibrous layer c. 30 nm thick was found around the outer-membrane surface, whereas no such structure was observed in the other group of isolates, most of which were from sputum. Lipopolysaccharides extracted from the isolates with a dense fibrous layer were found by SDS-PAGE to have long O-polysaccharide chains, whereas strains without such a layer mostly had lipopolysaccharides that lacked high mol. wt. O-polysaccharide chains.
Bacteremia↗
A comparative study of partial primary structures of the catalytic region of mammalian protein C.
Protein C (PROC) is a plasma vitamin K-dependent zymogen of a serine protease which regulates blood-clotting cascade through proteolytic inactivation of the non-enzymatic cofactors of blood coagulation, Va and VIIIa. We characterized the partial nucleotide and amino acid sequences for the catalytic domain of PROC in six mammalian species, rhesus monkey, dog, cat, goat, horse and mouse, and compared these sequences with known ones from humans, the bovine and rat. By using a pair of primers based on the nucleotide sequences from human and bovine PROC cDNA, the PROC gene fragments were enzymatically amplified from their genomic DNAs and were sequenced by the dideoxy-termination method. The cloned PROC gDNA encoded a part of the heavy chain of PROC including the lesions of active site residues corresponding to human PROC Asp-257 and Ser-360. Comparison of the sequences from these species revealed that there was a high degree of homology at the nucleotide and amino acid levels; from 69% to 96% of the amino acids in the catalytic region were identical among the nine species including humans, the bovine and rat. The locations of five Cys residues as well as the putative carbohydrate attachment sites were evolutionally conserved. All the amino acids recognized in the human abnormal PROC variants were conserved across species, suggesting their functional importance, and a comparison of the conserved residues among PROC from multiple species will provide considerable information in the investigations of PROC functions.
Amino Acid Sequence↗
Predominance of myeloid antigens in CD34-positive peripheral blood stem cells over those in bone marrow after administration of granulocyte colony-stimulating factor.
We analyzed the surface phenotype of CD34-positive (CD34+) cells in peripheral blood (PB) during the period of hematopoietic recovery following myelosuppressive chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34+ cells (45.8%, 37.8%, respectively) (both p < 0.01). In particular, the CD13 positivity of PB CD34+ cells harvested with granulocyte colony-stimulating factor (G-CSF) was significantly higher than that of those without G-CSF. Most of the PB CD34+ cells possessed the HLA-DR antigen, and less than 10% of the CD34+ cells coexpressed a mature cell antigen, such as CD14, GPA or Plt-1. The administration of G-CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and CD33+ 34+ cells (both p < 0.01). This G-CSF mobilization also resulted in an increased number of CD13- 34+ and CD33- 34+ cells and all types of colony-forming cells. On the other hand, macrophage colony-stimulating factor administration exerted little influence on the mobilization of PB CD34+ cells. Thus, G-CSF seemed to induce not only an expansion of circulating hematopoietic stem cells but also the myeloid differentiation of stem cells.
Adolescent↗
Analysis of the partial nucleotide sequences and deduced primary structures of the protease domains of mammalian blood coagulation factors VII and X.
In order to obtain sequence data for the blood coagulation factor VII and factor X in several mammalian species, we amplified and sequenced the DNA segments of exon VIII from each gene by means of the polymerase chain reaction (PCR) method. The DNA segments from the following species were successfully amplified: factor VII from the rhesus monkey and dog, and factor X from the rhesus monkey, Syrian hamster and rat. In each factor, the nucleotide sequences and predicted primary structures of the protease domain showed a high degree of homology among species; amino acid identities of approximately 68%-92% and 80%-98% were demonstrated among species in factor VII and factor X, respectively. The locations of the active site residues and five Cys residues were evolutionarily conserved in both factors. Interestingly, the amino acids involved in the human genetic variants, both factor VII 304-Arg and factor X 326-Arg, were always conserved across species. The data presented here will be helpful for investigating human genetic variants of factor VII or X, and will provide considerable information for constructing in vitro site-specific mutants of these factors.
Amino Acid Sequence↗
Granulocyte colony-stimulating factor does not enhance phagocytosis or microbicidal activity of human mature polymorphonuclear neutrophils in vitro.
The direct effects of human granulocyte colony-stimulating factor (hG-CSF) on mature polymorphonuclear neutrophils (PMNs) in vitro were studied with regard to chemotaxis, superoxide production, and phagocytosis and microbicidal activity against the following viable microorganisms: Staphylococcus aureus, serum-resistant Pseudomonas aeruginosa, and Candida albicans. Recombinant hG-CSF (rhG-CSF) acted as a chemoattractant for human PMNs in a dose-dependent manner. The chemotactic response of PMNs to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not enhanced by rhG-CSF at any of the concentrations used. rhG-CSF did not induce the generation of superoxide by itself. However, rhG-CSF was able to prime human PMNs and to enhance O2- release stimulated by FMLP in a dose-dependent manner. rhg-CSF did not enhance phagocytosis or killing of the three species of microorganisms by normal PMNs. With PMNs obtained from patients who had hematological disorders or solid tumors, no enhancement of the microbicidal activity was observed in most cases. Microbial killing mediated by PMNs depended on the ratio of PMNs to target organisms. We concluded from these facts that the most important effect of rhG-CSF was to increase the number of the peripheral PMNs and not to enhance the functions of mature PMNs.
Blood Bactericidal Activity↗
Effects of hydrocortisone on transmembrane currents in guinea pig ventricular myocytes--possible evidence for positive inotropism.
Steroid hormones are thought to have a positive inotropic action, but the precise electrophysiological effects which underlie this positive inotropism remain unknown. The effects of hydrocortisone on the L-type calcium current (ICa) of the isolated guinea pig ventricular cells were investigated under the whole-cell voltage-clamp recording. Hydrocortisone (10(-6) to 10(-5) M) increased the amplitude of ICa without any changes in the voltage-dependency in ICa. This agent retarded the fast inactivation component of ICa, but not the slow component. On the other hand, hydrocortisone slightly reduced the slope conductance of inward rectifying potassium current (IK1) at potentials less than -50mV. This effect on IK1 is favorable for the activation of ICa. Thus, these results indicate that the positive inotropism of hydrocortisone is mediated, at least in part, by a direct potentiating effect on ICa.
Animals↗
Thrombotic obstruction of the right coronary artery in a postoperative patient with Bland-White-Garland syndrome.
A 53-year-old female presented with symptoms of severe chest and back pain associated with oliguria. The patient had a history of exertional dyspnea since the age of 20, and easy fatigability since the age of 27. At the age of 41, she noted marked exacerbation of these symptoms after suffering from a cold and was ultimately diagnosed as having Bland-White-Garland (BWG) syndrome with mitral valve regurgitation. The patient then underwent re-implantation of an anomalous left coronary artery from the pulmonary artery to the posterolateral wall of the aorta. Eleven years later, she re-presented with symptoms of angina and congestive heart failure. Coronary angiography was subsequently performed and a total occlusion of the right coronary artery with probable thrombus was revealed. The right coronary artery was filled via collaterals from the implanted left coronary artery. Mitral regurgitation was noted during angiography. The patient underwent aorto-coronary artery bypass grafting of the right coronary artery and concomitant mitral valve replacement. Her postoperative condition remained excellent.
Coronary Angiography↗
The modulated receptor hypothesis revisited from the viewpoint of myocardial interstitial potential.
Time- and voltage-dependent interaction of antiarrhythmic agents with target cardiac ion channels is termed the modulated receptor hypothesis. Actually class I agents suppress the maximum upstroke rate (Vmax) of intracellular potential (Vic) depending on the pacing cycle length (PCL) and external potassium concentration ([K+]e). We examined this concept from the aspect of interstitial potential (Vis), since Vis reflects the second time derivative of Vic. Vic and Vis were recorded sequentially using standard microelectrode applied to the paced and superfused guinea pig papillary muscles. In the steady state, the greatest negative deflection of Vis (Vmin) was suppressed by quinidine (10 microM) in both PCL- and [K+]e-dependent manner, just like Vmax. However, quinidine-induced greater inhibition of Vmin than Vmax was evident at shorter PCL and greater [K+]e. Based on the sequential alteration of PCL and exposure to ouabain (10 microM), different quinidine sensitivity between Vmax and Vmin is most likely accounted for by the activity-dependent K+ efflux and Na(+)-K+ pump-mediated K+ uptake (i.e., [K+]e fluctuation). Thus, the modulated receptor hypothesis is concluded to be valid in terms of Vis.
Action Potentials↗
The c-kit molecule and the surface immunophenotype of human acute leukemia.
The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit molecule). Expression of the c-kit molecule on the gated leukemic blast cells from newly diagnosed patients with leukemia was analysed by flow cytometry using the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined, significant c-kit-positive blast cells were detected in 24 cases (69%), even though the percentage of positive cells was widely variable. The correlation between the percentage of cells positive for the c-kit molecule and the percentage of cells positive for CD34 was found to be statistically significant (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for lymphoid markers. The mean percentage of the cells expressing c-kit molecule among the lymphoid marker-positive cases was significantly larger than that among the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases were c-kit-negative, including 8 cases which were positive for some myeloid markers. Stem cell factor enhanced the colony growth in five out of six acute myeloblastic leukemia cases expressing the c-kit molecule. On the other hand, SCF did not stimulate colony growth in any of the four cases which were not positive for the c-kit molecule. These findings indicated that the distribution of flow cytometrically detectable c-kit molecules on leukemic cells is related to the morphologic and immunologic classification of these leukemic cells and to the expression of the CD34 cell surface molecule on some myeloid leukemic cells. On such cells, expression of the c-kit molecule may have a functional role and be related to the maturation process.
Adult↗
Successful second autologous blood stem cell transplantation after G-CSF-combined conditioning for the treatment of high-risk acute myelogenous leukemia.
We describe a patient with acute myelogenous leukemia (AML) who received his second autologous blood stem cell transplantation (ABSCT) following a G-CSF-combined pre-transplant conditioning regimen. The patient underwent ABSCT during first remission but suffered a relapse 8 months later. After achieving second remission, he was prepared for his second ABSCT; recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered in combination with Ara C, in addition to the same conditioning regimen as that used before the first ABSCT. There was no increase in regimen-related toxicity after this second G-CSF-combined conditioning regimen when compared with that observed after the first ABSCT. To date, the patient's second remission following the second ABSCT has lasted 26 months, which has exceeded that following the first ABSCT. The G-CSF-combined pretransplant conditioning regimen for ABSCT may be effective in the treatment of high-risk AML by increasing the chemosensitivity of the residual leukemic cells.
Adult↗
[CD7 positive acute myelogenous leukemia exhibiting pleural involvement as an initial manifestation].
A 51-year-old man had suffered from massive pleural effusion due to invasion of malignant cells. The analysis of bone marrow aspiration showed the proliferation of myeloperoxidase-positive blasts. The surface marker analysis of the blasts revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was diagnosed. The patient was treated with araC and daunorubicin as a remission induction therapy. Peripheral blood stem cells were harvested by leukapheresis after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU-GM were infused. Complete remission has been maintained for 8 months after autologous blood stem cell transplantation. Pleural involvement as an initial manifestation is rare in AML. Extramedullary growth of AML cells may be related to their immaturity, indicated by the expression of the cell surface antigens.
Antigens, CD↗
[A comparative study of imipenem/cilastatin sodium BID vs QID in the treatment of infections associated with hematopoietic disorders].
Using the envelope method, we allocated 125 patients with infections accompanied by hematopoietic disorders into two groups treated with imipenem/cilastatin sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were 54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0% (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID, efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No significant difference in response rates were observed between the two groups. 3. Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21 strains, in group QID. The eradication rates after treatment with IPM/CS was 100% in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients in group BID and 3 in group QID. Laboratory examination revealed abnormal values in 9 patients in group BID and 6 in group QID. However, all of the side effects disappeared after the suspension or discontinuation of IPM/CS. The efficacies of IPM/CS therapy for severe infections in patients with hematopoietic disease were similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.
Adult↗
Mutations in the transcriptional regulatory region of the precore and core/pregenome of a hepatitis B virus with defective HBeAg production.
Termination mutations in the precore open reading frame of hepatitis B virus (HBV) variants with defective hepatitis B e antigen (HBeAg) production have been demonstrated in both infected patients who have seroconverted to anti-HBe and those with fulminant hepatitis B. A donated plasma sample was found to be positive for the hepatitis B surface antigen, but negative for both HBeAg and anti-HBe. The HBV DNA titer in the plasma was estimated to be 32 pg/ml, and circulating virus-like particles were observed by electron microscopy. The entire nucleotide sequence of the virus was determined and at least 7 nucleotides were found to be unique when compared with previously reported sequences. These nucleotides created no termination codon in the precore/core, pol, preS/S and HBx open reading frames. The deduced amino acid substitutions were 28 Arg--Gln, 94 His--Tyr, 131 Val--Ile and 132 Phe--Tyr of HBx and 715 Met--Val and 789 Asp--Asn of pol. Furthermore, the precore and core/pregenome promoter contained altered 1764 A, 1766 T and 1768 A. Therefore, mutations in regions other than the precore open reading frame can cause defective HBeAg production.
Adult↗
Myasthenia gravis after allogeneic bone marrow transplantation.
A 37-year-old Japanese man with chronic myeloid leukemia (CML) developed myasthenia gravis 29 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched brother. Proximal muscle weakness and bilateral ptosis occurred along with the exacerbation of chronic GVHD shortly after sudden cessation of cyclosporine (CYA) and prednisolone. The diagnosis of myasthenia gravis was made based on clinical symptoms and elevation of an anti-acetylcholine receptor antibody titer and all symptoms related to myasthenia gravis promptly diminished with the start of treatment for chronic GVHD. In most previously reported cases, the underlying disease was aplastic anemia (6 of 7 cases) and donors were of the opposite sex (6 of 7 cases). The haplotypes HLA B7 (3 of 5 cases), B35 (3 of 5 cases), and DR2 (3 of 3 cases) were common. All cases suffered from chronic GVHD. The present case had only chronic GVHD and HLA B7 as a background for myasthenia gravis after BMT. The abrupt cessation of immunosuppressive therapy may also be related to the development of myasthenia gravis after BMT.
Adult↗
[A case of advanced gastric cancer complicated with multiple liver metastasis successfully treated with l-LV and 5-FU combination].
A 65-year-old man complaining of nausea and loss of appetite was diagnosed as having Borrmann type 3 gastric cancer with multiple liver metastasis. He was treated for 5 days with bolus injections of l-leucovorin (l-LV: 100 mg/m2/day) followed by 5-fluorouracil (5-FU; 370 mg/m2/day), and this was repeated every 4 weeks. The computed tomography scan after 3 cycles showed an approximately 70% decrease in the size of metastatic lesions, indicating a partial response. The primary gastric lesion also showed a partial response. There were modest but tolerable side effects such as diarrhea. After 3 cycles, the patient was discharged and was given oral 5-FU preparation. He died 9 months after initial chemotherapy with a response duration of 5 months. This l-LV and 5-FU combination therapy appears useful for advanced gastric cancer.
Aged↗