Characteristics of membrane currents in single rat myometrial cells.
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Animals↗
Biomedical subjects
H Miyoshi
Publications and source records attributed to H Miyoshi.
Immunological determination of fecal hemoglobin and transferrin levels: a comparison with other fecal occult blood tests.
Immunological determination of fecal hemoglobin and transferrin levels was performed in inpatients on an unrestricted diet, including patients with colon cancer or polyps and a control group. When hemoglobin levels of 5.1 micrograms/g feces and transferrin levels of 0.4 microgram/g feces were designated as positive, 48 of the 60 fecal specimens from colon cancer patients were positive. This result was significantly superior to that for another fecal occult blood immunological test (FECA-EIA) (p less than 0.005), and similar to the results of two chemical tests (guaiac and Hemoccult). Twenty-eight of the 78 fecal specimens from patients with colonic polyps were positive, again a result superior to the FECA-EIA (p less than 0.005) and similar to the chemical tests. Three of the 99 control fecal specimens were positive, which was a similar result to that obtained with the FECA-EIA and significantly superior to the chemical tests (both p less than 0.005). Thus, combined detection of fecal hemoglobin and transferrin levels can be used as a fecal occult blood test in patients without dietary restriction.
Aged↗
t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1.
The t(8;21)(q22;q22) translocation is a non-random chromosomal abnormality frequently found in patients with acute myeloid leukemia (AML) with maturation (M2 subtype). We report here the cloning of a gene, named AML1, on chromosome 21 that was found to be rearranged in the leukemic cell DNAs from t(8;21) AML patients. The breakpoints in 16 out of 21 patients were clustered within a limited region of AML1, and detailed analysis in 3 patients revealed that the breakpoints occurred in the same intron of the gene. Sequencing of cDNA clones identified a long open reading frame encoding a 250-amino acid protein. Northern blot analysis detected four constant mRNA species in t(8;21) leukemic and normal cells; the largest species was more abundant in the leukemic cells than in normal cells. In addition, two mRNA species limited to the leukemic cells were found. These findings indicate that the AML1 gene may be involved in neoplastic transformation of AML with the t(8;21) translocation.
Acute Disease↗
Inhibition of electron transport of rat liver mitochondria by unnatural (-)-antimycin A3.
The inhibition of electron transport by unnatural (-)-antimycin A3 was examined with rat liver mitochondria and compared with that of natural (+)-antimycin A3. (-)-Antimycin A3 inhibited respiration about 1/100th as strongly as natural (+)-antimycin A3. (-)-Antimycin A3 binding to the cytochrome bc1 complex did not seem to induce a conformational change in this proteinous complex. The binding site of (-)-antimycin A3 was probably the same as that of (+)-antimycin A3 (at the Qi center). However, the mode of interaction with the Qi center by (-)-antimycin A3 and (+)-antimycin A3 was somewhat different.
Animals↗
Electron transport inhibition of the cytochrome bc1 complex of rat-liver mitochondria by phenolic uncouplers.
The respiration inhibition of rat-liver mitochondria by a series of substituted phenolic uncouplers was studied. The inhibitory effects were classified into three types, I-III, depending on the pattern of the changes in inhibitory potency observed when the potent uncoupler SF6847 was simultaneously applied. The extent of inhibition by type I phenols did not change as the transmembrane potential was dissipated by SF6847, but the extent of inhibition by type II and III phenols was decreased and increased, respectively. With the addition of another potent uncoupler, fluazinam, the uncoupling activity of which disappears with time, the inhibitory potency of type II phenols was decreased, but increased reversibly with the disappearance of the uncoupling effect of fluazinam. However, the inhibitory potency of type III phenols increased by fluazinam was not reduced. The inhibitory site of the phenols studied here was the cytochrome bc1 complex. This complex undergoes conformational changes when the transmembrane potential changes. The findings suggested that inhibition by substituted phenolic uncouplers depends partially on conformational changes of the cytochrome bc1 complex that accompany variations in the transmembrane potential.
Animals↗
Molecular assignment of a translocation breakpoint in acute myeloid leukemia with t(8;21).
An 8;21 translocation is a common chromosome abnormality associated with acute myeloblastic leukemia with maturation (M2 of French-American-British (FAB) classification). We have isolated chromosome 21 Notl linking clones; pulsed field gel electrophoresis analysis with one clone (LL263) detected an altered fragment of Notl-digested leukemic cell DNA carrying t(8;21). The altered fragment was shown to be produced by the 8;21 translocation. The breakpoint in chromosome 21 was located about 13 kb to 100 kb proximal to the LL263 Notl site. Because the LL263 clone has a CpG island and is a short distance from the breakpoint, the clone itself may be considered as a candidate for part of the t(8;21) associated gene.
Acute Disease↗
Electrophysiological properties of membrane currents in single myometrial cells isolated from pregnant rats.
The whole-cell voltage-clamp method was applied to single smooth muscle cells prepared from the longitudinal layer of the pregnant rat myometrium (17-20 days of gestation). It was found that the transient inward current mainly consists of Ca2+ current, because the removal of Ca2+ ions from the external medium and 10 microM nifedipine eliminated this inward current. Its steady-state inactivation curve was obtained by the standard method, in which the membrane potential of half inactivation and the slope factor were estimated to be -58.0 +/- 4.9 mV (n = 11) and 8.9 +/- 1.4 mV (n = 11), respectively. In a small number of preparations (in 2 out of 30 preparations), there remained a very fast inward current in Ca(2+)-free medium containing Mg2+. Tetrodotoxin (TTX, 10 microM) can can abolish this current, suggesting that the channel for this current is equivalent to the Na+ channel in nerve cells. Two major phases of outward currents were identified by voltage jumps from negative holding levels to more positive levels. The first phase was a fast transient outward current. This current remained intact after external tetraethylammonium (TEA, 20 mM) was added. Following the transient current, a large delayed rectified outward current reached its peak over a period of 50 ms and then decayed. The reversal potential for this outward current was determined by observing the change of polarity of the tail currents with the change in extracellular K+ concentration [( K+]o). The slope for the change of reversal potential per ten-fold change in [K+]o is 57.7 mV at more than 23.2 mM [K+]o, indicating that this current is mostly carried by K+ ions. Voltage-dependent inactivation of the delayed rectified outward current was determined by the standard method. The membrane potential for half inactivation and the slope factor were estimated to be -42.8 +/- 3.9 mV (n = 3) and 10.1 +/- 1.5 mV (n = 3), respectively. External TEA (20 mM) effectively eliminated the delayed rectified outward currents. Nifedipine (10 microM) suppressed not only Ca2+ current but also outward K+ currents.
Animals↗
Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. I. Clinical aspects.
The levels of human hepatocyte growth factor (hHGF) in sera obtained from patients with various liver diseases were determined using adult rat hepatocytes maintained in primary culture. The mean hHGF activity for 22 patients with fulminant hepatic failure was about nine times greater than that found in normal human serum. The increase in serum hHGF activity seen in two patients with "acute-on-chronic" hepatitis was similar to that found in patients with fulminant hepatic failure. The serum level of hHGF from patients with acute hepatitis is related to the stage of their illness. The average value for 31 patients was about three times that of normal human serum. In some patients, the time course for the increase in serum hHGF activity was similar to that demonstrated for alpha-fetoprotein. The mean hHGF activity in serum for the 33 patients with chronic hepatitis and from 25 patients with liver cirrhosis was increased also compared with that of normal human serum. In addition, serum hHGF activity in three of seven patients studied after partial hepatectomy for a space-occupying lesion of the liver was increased. These data suggest that the increase in serum hHGF activity present in patients with various liver diseases reflects a self-defense mechanism that is involved in the process of liver cell regeneration.
Growth Substances↗
Clinical study of a new fecal occult blood test using a combination assay of hemoglobin and transferrin.
The applicability of a new immunological fecal occult blood test in which hemoglobin (Hb) and transferrin (Tf) are simultaneously assayed was evaluated. The mean absorbance and standard deviation (510/630 nm) obtained by this test was 0.840 +/- 0.805 in 51 fecal samples from patients with colon cancer, 0.248 +/- 0.305 in 95 samples from patients with colon polyps, and 0.104 +/- 0.053 in 110 samples from control patients; these values differed significantly (P less than 0.005). Hb and Tf concentrations were separately determined in the same fecal samples, and qualitative evaluation was performed with a cutoff value of 5.1 micrograms/g feces for Hb and 0.4 micrograms/g feces for Tf. Hb or Tf was positive in 41 of the 51 samples in the colon cancer group, 33 of the 95 in the colon polyp group, and 3 of the 110 in the control group. Qualitative analysis of the values obtained by the combination assay of Hb and Tf with a cutoff value of 0.200 revealed positive rates of 41/51 in the colon cancer group, 33/95 in the colon polyp group, and 4/110 in the control group. These results suggest the usefulness of a combination assay of Hb and Tf as a fecal occult blood test.
Aged↗
[Combination of transarterial chemoembolization and endocrine therapy for liver metastases of breast cancer].
Nine patients with multiple metastases including liver from breast cancer were treated with transarterial chemoembolization through hepatic artery using 40-50 mg of 4'-epi-adriamycin and Lipiodol, followed by 800-1,200 mg/day of medroxyprogesterone acetate. Of 9 patients thus treated, there were 4 partial response (44%), 2 no change and 3 progressive disease. Duration of disease control ranged from 4 to 46 months (mean 24.5 months). Seven out of 9 patients died within 6 to 37 months (mean 15.3 months) after diagnosis of liver metastases. The 3- and 5-year survival rates were 45% and 11%, respectively. We conclude that this therapy is a useful treatment modality for controlling liver metastases of breast cancer.
Adult↗
Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion.
In this study we have assessed the hypothesis that there is a postreceptor defect in glucose metabolism that makes the severely burned patient unable to oxidize glucose efficiently as an energy source. The intracellular pyruvate pool was labeled by the infusion of 3-13C-lactate, and expired CO2 production and isotopic enrichment of both pyruvate and CO2 were determined to calculate the rate of pyruvate production and oxidation. 6,6-d2-Glucose and 15N-alanine were infused simultaneously to relate pyruvate kinetics and oxidation to glucose and alanine kinetics. Five normal volunteers and 10 severely burned patients (mean of 80% +/- 5% body surface burned) were studied in the basal state and during continuous (unlabeled) glucose infusion. Also, the effect of dichloroacetate, which normally stimulates pyruvate dehydrogenase activity, was assessed in both volunteers and patients. The burned patients had many of the classic metabolic responses to severe injury, including significant increases in resting energy expenditure, glucose production, and alanine release from protein breakdown. However, rather than being inhibited, the rate of pyruvate oxidation was increased approximately 300% in burned patients. Although the patients had an elevated mean concentration of lactate, stemming from increased lactate production, no deficit in pyruvate dehydrogenase activity was evident. Rather, the high rate of lactate production was apparently a consequence of the high rate of glycolysis. On the other hand, the direct pathway for synthesis of glycogen from infused glucose appeared to be impaired in burned patients. In both volunteers and patients, dichloroacetate stimulated the percent of pyruvate directed to oxidation, thereby reducing the conversion of pyruvate to other fates, including lactate. However, because there was no deficit in pyruvate dehydrogenase activity in the patients compared with normal volunteers before dichloroacetate treatment, no unique effect of dichloroacetate on glucose or protein kinetics was observed in burned patients. From these results we conclude that if there is a postreceptor defect in glucose metabolism in burned patients, it involves the pathway of direct glycogen synthesis and not the pathway of oxidation.
Absorption↗
Haptoglobin prevents renal dysfunction associated with intravariceal infusion of ethanolamine oleate.
Endoscopic injection sclerotherapy (EIS) with ethanolamine oleate was performed in patients with esophageal varices either with (18 patients) or without (19 patients) pretreatment with haptoglobin. The serum levels of urea nitrogen, creatinine, and beta 2-microglobulin, the creatinine clearance, and the urinary levels of N-acetyl-beta-D-glucosaminidase and urinary beta 2-microglobulin were measured before and after EIS. Indices of the glomerular filtration rate (serum levels of urea nitrogen, creatinine, beta 2-microglobulin; creatinine clearance) showed no significant changes after EIS in either the haptoglobin-treated or untreated groups. However, the increase in the urinary parameters after EIS (which are indices of renal tubular function) was suppressed in the haptoglobin-treated group (p less than 0.005 for urinary beta 2-microglobulin). Our results indicated that the administration of haptoglobin has a prophylactic effect on renal tubular dysfunction associated with the use of ethanolamine oleate in EIS.
Acute Kidney Injury↗
Changes in thrombin-antithrombin III complex after endoscopic injection sclerotherapy.
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Antithrombin III↗
Immunochemical detection of human blood in feces.
We have developed a new immunochemical test for fecal occult blood utilizing enzyme-linked immunosorbent assay (ELISA) of human hemoglobin (HbAo) and transferrin (Tf) simultaneously. The ELISA had a sensitivity of about 15 ng/ml Hb, and the measurable range was 1.5-750 micrograms Hb per g feces. The stability of Tf in feces was greater than that of Hb. In 17 out of 18 patients with colon cancer, 8 out of 15 patients with colon polyps, and 11 out of 20 patients with upper-gastrointestinal disorders. The Hb and Tf values were more than 10 micrograms/g feces, in terms of Hb concentration. The ELISA for human fecal HbAo and Tf might be useful for the diagnosis of gastrointestinal disorders.
Animals↗
Quantitative analysis of uncoupling activity of substituted phenols with a physicochemical substituent and molecular parameters.
The uncoupling potency of a series of substituted phenols with rat-liver mitochondria was analyzed quantitatively with physicochemical substituent and molecular parameters such as log P, P being the partition coefficient in a phosphatidylcholine liposome/water system, log KA, KA being the acid dissociation constant, and the Taft-Kutter-Hansch steric constant, Es, for ortho-substituents. The potency evaluated from the concentration in the medium required for a defined response was analyzed, showing that the incorporation of compounds in terms of log P, a certain balance between neutral and ionized forms expressible by a parabolic function of log KA and the steric shielding effect of the ortho-substituents on the negatively charged center of ionized form are highly significant factors governing the variations in potency. The potency was also quantitatively separated into the intrinsic potency as the protonophore inside the inner mitochondrial membrane and the incorporation factor in terms of log P. Some phenols found as outliers from the correlations and some others distorting the quality of the correlations were shown to have inhibitory effects on the respiratory chain by specific and non-specific modes of action, respectively, besides uncoupling activity.
Animals↗
Bradykinin attenuates glucagon-induced leucine oxidation in humans.
Trauma and injury are associated with accelerated protein loss. Counterregulatory hormones are possible mediators of this response. In the present study, the effect of glucagon and glucagon plus bradykinin on leucine and urea kinetics was examined in nine normal volunteers during somatostatin infusion and basal insulin replacement. Bradykinin was given because of its prostaglandin-stimulating qualities and the potential anabolic action of prostaglandins. Physiological hyperglucagonemia elicited a small but significant reduction of total leucine flux and rate of urea synthesis. Simultaneously, leucine oxidation increased by 70%. The simultaneous infusion of bradykinin did not alter glucagon-related changes in urea or leucine kinetics. Bradykinin, however, significantly attenuated the stimulation of leucine oxidation by glucagon. These results suggest that glucagon and tissue factors are involved in controlling leucine metabolism in humans.
Adult↗
Alteration of natural killer cell subsets (two color analysis) and their activity in peripheral blood in inflammatory bowel disease.
The natural killer (NK) activity and NK cell subsets in peripheral blood were evaluated in patients with inflammatory bowel disease (IBD), by using 51Cr release cytotoxicity assay and two color flowcytometry analysis. The peripheral blood NK activity was significantly lower in IBD than that in normal controls. This decrease of the NK activity was independent on the disease activity of IBD but dependent on the steroid medication. The total population of NK cells (Leu 7+ or 11c+ cells) did not change in IBD as compared with those of normal controls. However, the proportions of Leu7+11c- cells and Leu7-11c+ cells in IBD were higher and lower, respectively as compared with those of normal controls. These findings suggest that the maturation step of NK cell lineages might be impaired in IBD. The decrease of NK activity in IBD was supported by the change in the proportion of NK cell subsets described above. It was thought that such a change in NK cell subsets might be a specific finding in IBD patients, because it was not observed in patients with non-IBD colitis.
Adult↗
[Study on the usefulness of haptoglobin used on endoscopic injection sclerotherapy].
The effect of haptoglobin (Hp) used on endoscopic injection sclerotherapy (EIS) was evaluated by examining the increase of serum free hemoglobin (FHb) and the changes of renal function. In control group, the increase of serum FHb (delta FHb) was paralleled with the volume of 5% ethanolamine Oleate (EO) injected intravariceally, and free Hp (FHp) was disappered in this group soon after EIS. On the contrary, in the group treated with Hp, neither the increase of FHb nor decrease of FHp were recognized. The significant increase of urine beta 2 microglobulin and NAG was recognized in control group. Therefore, if Hp is used at initial EIS, it would be prevented that serum FHb due to intravascular hemolysis increases, consequently the possibility of renal dysfunction.
Adult↗