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K Horikawa

Publications and source records attributed to K Horikawa.

At least 73 records · Page 4Linked to original sources

[Plasma proteins].

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Blood Protein Electrophoresis↗

Persistence of affected T lymphocytes in long-term clinical remission in paroxysmal nocturnal hemoglobinuria.

Long-term clinical remission of more than 10 years is rarely seen in paroxysmal nocturnal hemoglobinuria (PNH). Affected blood cells in PNH lack glycosylphosphatidylinositol (GPI)-anchored membrane proteins such as decay-accelerating factor (DAF) and CD59. We performed a flow cytometric analysis of circulating blood cells obtained from two patients with PNH who had been in clinical remission for more than 10 and 25 years, respectively. Affected cells with the PNH phenotype were demonstrated only among T-lymphocytes. Persistent affected T cells were negative for the CD52 protein only, this protein being a GPI-anchored lymphocyte marker without complement regulatory activity. The persistence of the affected T cells may be explained either by an inherently long life span after the disappearance of the PNH stem cell or by insidious production at a subclinical level by affected stem cell. In either event, detection of affected T cells, especially CD52-negative T cells, may be useful for the evaluation of long-term clinical remission in PNH.

Adrenal Cortex Hormones↗

Degree of fatty acyl chain unsaturation in biliary lecithin dictates cholesterol nucleation and crystal growth.

To clarify factors involved in the formation of cholesterol gallstones, we studied the relationship between the degree of fatty acyl chain unsaturation of biliary lecithin and bile metastability. We used supersaturated model bile solutions (molar taurocholate/lecithin/cholesterol ratio (73:19.5:7.5), total lipid concentration 9 g/dl) that contained equimolar egg yolk or soybean lecithins or a sn-1 palmitoyl, sn-2 linoleoyl phosphatidylcholine. Gel permeation chromatographic studies showed that the vesicular cholesterol distribution and dimension were inversely related to the degree of unsaturation of the lecithin species, estimated by reverse phase, high-performance liquid chromatography. Differential interference contrast microscopy and assay of cholesterol crystal growth showed that a higher degree of fatty acyl chain unsaturation of the lecithin species was associated with a faster nucleation time and rate of crystal growth. Our results suggest that vesicular lecithins containing more unsaturated fatty acyl chains bind less tightly to cholesterol than lecithins containing predominantly saturated fatty acids, and that the biliary lecithin species dictates, in part, the nucleation and growth of cholesterol crystals in bile.

Bile↗

Interleukin-2-dependent T-cell lines established from paroxysmal nocturnal hemoglobinuria patients.

Peripheral blood T lymphocytes obtained from two patients with paroxysmal nocturnal hemoglobinuria (PNH) were immortalized with human T-lymphotropic virus type 1 (HTLV-1). These cells showed interleukin-2 (IL-2)-dependent cell growth in culture. Cell surface analysis showed that they had the phenotype of a helper/inducer T subset that was positive for CD2, CD3, and CD4, but negative for CD8, similar to adult T-cell leukemia cells induced by HTLV-1. These cell lines lacked glycosylphosphatidylinositol (GPI)-anchored proteins, CDw52, CD55 (decay-accelerating factor; DAF), and CD59 on the cell surface, whereas intracellular DAF protein was detected. These T-subset cell lines with a PNH phenotype did not synthesize GPI anchor, whereas a control cell line, similarly prepared from the T cells of a healthy volunteer, produced the anchor. The control cells expressed CDw52, DAF, and CD59 on the cell surface and showed the phenotype of a helper/inducer subset. Southern blot analysis confirmed the clonality of each cell line. These CD4+ T-cell lines with a PNH phenotype and a subset-matched control counterpart could be a useful model for PNH investigation.

Antigens, CD↗

Simultaneous microanalysis of biliary cholesterol, bile acids and fatty acids in lecithin using capillary column gas chromatography: an advantage to assess bile lithogenecity.

Simultaneous determination of biliary lipids was performed by alkaline hydrolysis, the formation of the methyl ester derivatives of fatty acids that are constituents of phospholipids and of the acetylated methyl ester derivatives of bile acids, and subsequent analysis by capillary column gas chromatography. Complete separation and satisfactory recovery of cholesterol, bile acids, and fatty acids were achieved. Also, the accuracy of the calculation of the bile cholesterol saturation index was enhanced by computation. Since the degree of acyl chain unsaturation affects the cholesterol-holding capacity in vesicles, this method provides a unique insight into bile metastability by the quantitative assessment of fatty acids in lecithin.

Bile↗

Moderate inhibition of mutagenicity and carcinogenicity of benzo[a]pyrene, 1,6-dinitropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs.

The activity of six Chinese medicinal herbs against the environmental mutagens and carcinogens benzo[a]pyrene (B[a]P), 1,6-dinitropyrene (1,6-diNP) and 3,9-dinitrofluoranthene (3,9-diNF) was determined. Samples of Prunella spica, Rheum palmatum, Polygonum multiflorum, Agrimonia pilosa, Ephedra sinica and Teitoutou were tested in an in vitro system. Antimutagenic activity against B[a]P was marked in the presence of extracts (boiled for 2 h in a water bath) whereas that against 1,6-diNP and 3,9-diNF varied from 20 to 86%. The differences in inhibition might be due to inactivation of metabolic enzymes. An extract of P. multiflorum was divided into ether, ethyl acetate and water soluble fractions, which were tested for antimutagenic activity against B[a]P. The antimutagenic action of the ethyl acetate soluble fraction was substantial and dose-dependent. Tannins and related compounds were the major components of the extract, of which epigallocatechin, epigallocatechin gallate, epicatechin gallate and tannic acid strongly inhibited the mutagenicity of B[a]P (2.5 micrograms/plate) in Salmonella typhimurium TA98 with S9 mix. To confirm the results of the in vitro test system, F344/DuCrj male rats were given a subcutaneous injection of B[a]P. Thereafter, they received water extracts of the six Chinese medicinal herbs for 50 weeks and were examined for tumors. The P. multiflorum extract significantly reduced the tumor incidence.

Animals↗

Stenotic lesions in vascular access: treatment with transluminal angioplasty using high-pressure balloons.

In our institute, one hundred sixty-four balloon dilatations of stenotic lesions in vascular access have been performed since November 1991. All of these procedures were done with high-pressure balloon catheters. In addition to seventy-four cases treated with only percutaneous transluminal angioplasty, there were thirty-four cases which were treated by thrombectomy and/or surgical revision with subsequent intraoperative balloon angioplasty. These angioplastic procedures were initially successful in 142 (87%) of 164 stenoses. The patency rate after 3 months was 68%; after 6 months, 42%; and after 1 year, 25%. There were no serious adverse reactions in our series. This procedure can be safely done with minimal traumatization and, although long-term patency rates are low, repeated dilatations can be performed with ease, when restenosis occurs, to keep a fistula functioning for a long time in appropriate patients.

Angioplasty, Balloon↗

Partial characterization of mechanism(s) by which sulphobromophthalein reduces biliary lipid secretion.

This study was performed to explore the mechanisms by which sulphobromophthalein (BSP) reduces the secretion of biliary lipid using Sprague-Dawley rats (SDR) and mutant rats with congenital conjugated hyperbilirubinaemia bred from SDR (EHBR). We infused the bile-salt-pool-depleted rats with sodium taurocholate at a constant rate of 160 nmol/min per 100 g body wt. with BSP (12.5, 25 and 50 nmol/min per 100 g body wt.) or BSP-GSH (12.5, 25 and 50 nmol/min per 100 g body wt.). The biliary secretion of BSP and BSP-GSH was markedly impaired in EHBR as compared with that in SDR. BSP reduced the biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting the secretion of bile salts and composition of fatty acids in phospholipids in SDR, but had no effect on lipid secretion in EHBR. In contrast, BSP-GSH had no such effect on biliary lipids, either in the SDR or EHBR. In addition, the amount of BSP in the liver of EHBR was in the same range as that of SDR. Therefore it is unlikely that an intracellular mechanism is involved in the phenomenon of uncoupling by BSP. We conclude that the uncoupling of biliary lipids from bile-salt secretion by BSP occurs at the level of the bile canaliculus following the secretion of unconjugated BSP.

Animals↗

Impaired glycosylation of glycosylphosphatidylinositol-anchor synthesis in paroxysmal nocturnal hemoglobinuria leucocytes.

Metabolic labeling with [3H]sugars in vivo or [3H]sugar nucleotides in vitro of glycosylphosphatidylinositol (GPI)-anchor precursors in peripheral blood granulocytes and cultured T lymphocytes of paroxysmal nocturnal hemoglobinuria (PNH) patients showed a synthetic defect in the GPI-anchor. Among the GPI-anchor precursors, phosphatidylinositol (PI) was normally synthesized, while the synthesis of glucosaminylphosphatidylinositol (GlcN-PI) and subsequent mannosylation of GlcN-PI were inhibited in affected cells. The defect in the GPI-anchor synthesis in PNH is thus attributed to interrupted glycosylation at plural sites in the synthesis of the common carbohydrate structure of the anchor.

Carbohydrate Sequence↗

Expression of decay-accelerating factor and CD59 in lymphocyte subsets of healthy individuals and paroxysmal nocturnal hemoglobinuria patients.

The expression of phosphatidylinositol (PI)-anchored complement-regulatory membrane proteins on circulating blood cells has been well clarified; however, the PI proteins on lymphocyte subsets have not been fully analyzed yet. We examined the expression of decay-accelerating factor (DAF) and CD59 on the T lymphocytes (CD2+, CD3+, CD4+, and CD8+) and CD20+ B lymphocytes in ten healthy volunteers and 12 paroxysmal nocturnal hemoglobinuria (PNH) patients by cytofluorometry. In healthy controls, each subset of lymphocytes showed a small population of cells weakly positive and a large population of cells strongly positive for DAF and CD59, while erythrocytes showed a single population of cells positive for the PI proteins. The two-population expression of DAF was most distinctive in CD8+ T cells among the subsets. In PNH, each subset of lymphocytes showed a moderately higher population of cells weakly positive and a smaller population of cells strongly positive for the membrane proteins compared with those in the healthy controls. Moreover, in some PNH cases, a negative population for the proteins was found in all subsets. Thus the analysis of PI-anchored proteins on lymphocytes subsets (especially CD8+ T cells) was considered to be of diagnostic value in PNH patients who receive blood transfusion after hemolytic attack of affected erythrocytes. Furthermore, the two-population expression of PI proteins in normal lymphocytes suggests that membrane PI protein would be a new subset marker of lymphocytes.

Adult↗

Chromosomal aberrations induced in vitro by 3,7- and 3,9-dinitrofluoranthene.

The chromosomal aberration test using a Chinese hamster cell line (CHL) was carried out with 3,7- and 3,9-dinitrofluoranthene (DNF) with and without exogenous metabolic activation (rat liver S9 mix). The highest dose tested was limited to 20 micrograms/ml because of the compounds' insolubility in dimethyl sulfoxide. Both DNFs induced chromosomal aberrations in the absence of S9 mix; the frequency was not very high. Results were reproducible, but without clear dose-response relationships. Neither DNF induced chromosomal aberrations in the presence of S9 mix. Both DNFs did not induce polyploid cells under any conditions.

Aneuploidy↗

The presence of mutagens/carcinogens in the excised lung and analysis of lung cancer induction.

To elucidate a relationship between lung cancer and tumor induction of environmental chemicals, the presence of 1-nitropyrene (1-NP) and benzo[a]pyrene (B[a]P) in 137 Japanese (97 male and 40 female), and 21 Chinese lung specimens was examined by HPLC, and GC-MS and environmental exposure discussed. Mortality due to lung cancer in Fuyuan County, China, is much higher than that of other cancers. We investigated 21 patients who were residents of Fuyuan County. All were female aged 28-64 years and were non-smoking farmers and cooks. The histological features of the tumors were adenocarcinoma, squamous cell carcinoma and small cell carcinoma. The incidence of cancer was due to inhaling soot from the combustion of coal used for cooking and indoor heating. The polycyclic aromatic hydrocarbons, chrysene, benzo[k]fluoranthene, B[a]P, benzo[g,h,i]perylene and pyrene, but not their nitrated derivatives, were detected in substantial amounts in the resected lungs. These mutagens and carcinogens normally originate in combustion products of coal, and are discussed as the possible initiators of the tumors in the lungs of these patients. All the Japanese lung specimens were also obtained from non-smokers. The concentrations of 1-NP averaged 21.3 +/- 12.4 and 5.9 +/- 2.4 pg/g of Japanese and Chinese samples respectively. The concentrations of B[a]P averaged 180.2 +/- 103.7 and 608.7 +/- 477.1 pg/g of Japanese and Chinese samples respectively. Thus, Japanese and Chinese lung specimens were mainly contaminated by 1-NP and B[a]P, respectively. Typical tissues from a carcinomatous human lung were examined. The patient was a 64-year-old Japanese male non-smoker and farmer who had raised chickens over a period of 40 years. The histological features of the tumor were those of keratinizing squamous cell carcinoma. 1-Nitropyrene, 1-nitro-3-hydroxypyrene, 1,3-dinitropyrene and chrysene were detected at concentrations of 0.11, 0.036, 0.095 and 0.16 ng respectively per gram of lung tissue. This cancer was due to long-term exposure to the combustion products of heavy oil used in a chicken house.

Adenocarcinoma↗