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Biomedical subjects

S Eto

Publications and source records attributed to S Eto.

At least 127 records · Page 7Linked to original sources

Enhancing effects of IL-2 on M-CSF production by human peripheral blood monocytes.

Monocytes have the capacity to produce granulopoietic factors such as M-CSF and G-CSF. Our findings here showed that interleukin-2 (IL-2), at a concentration of more than 0.05 ng/ml, led to a 12-fold increase in the production of M-CSF in the human peripheral blood mononuclear cells after 72 h incubation compared to the control culture. Even in purified monocyte cultures with added IL-2, a 3-fold increase in M-CSF production was observed at an IL-2 concentration of 50 ng/ml. The enhancing effect of IL-2 on M-CSF secretion was also observed when IL-2-stimulated non-phagocytic cell-conditioned medium was added to monocyte cultures. These results indicated that IL-2, both directly and indirectly, activated monocytes to enhance the production of M-CSF. In addition, the expression of IL-2 receptor (CD25) on monocytes was more enhanced in cultures containing IL-2 than in cultures without IL-2. On the other hand, IL-2 did not induce G-CSF production in purified monocytes. These in vitro results suggest that when IL-2 is used clinically, the various biological activities of M-CSF should also be taken into consideration.

Cells, Cultured↗

Effects of recombinant human erythropoietin (EPOCH) on the coagulation and fibrinolytic systems and platelet function in pre-dialysis patients with chronic renal failure.

The purpose of this study was to investigate whether or not the systems of coagulation and fibrinolysis are activated after human recombinant erythropoietin therapy in patients with end-stage renal failure and renal anemia. Six thousand IU of human recombinant erythropoietin (EPOCH) were administered intravenously to 11 patients once a week for 8 weeks. Coagulation, fibrinolysis and platelet as well as renal functions were investigated before and after the EPOCH therapy. Platelet count did not increase in spite of improvement in anemia. No changes in prothrombin time, activated partial thromboplastin time, concentrations of fibrinogen, fibrinopeptide A, thrombin antithrombin III complex, fibrin/fibrinogen degradation products (FDP), FDP-E, FDP-D dimer, plasmin alpha 2-plasmin inhibitor complex were observed. Platelet factor 4 and beta-thromboglobulin also were unchanged. Reciprocal changes in serum creatinine concentrations over the duration of therapy were compared before and after therapy. There was no significant difference between the reciprocal changes in serum creatinine concentrations before and after therapy. The increases in hemoglobin did not correlate with the changes in coagulation, fibrinolysis and the other parameters, except for the change in prothrombin time. These results indicate that coagulation, fibrinolysis and platelet systems in end-stage renal failure patients were not affected by EPOCH administration, in spite of increase in hemoglobin.

Adult↗

[Medical treatment of malignant hypercalcemia].

Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent medical treatments are needed since malignant hypercalcemia progresses very rapidly. The intravenous administration of sufficient quantities of isotonic saline sometimes with loop diuretic agents is the first and fundamental step in the management of malignant hypercalcemia. As hormonal therapeutic agents for malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual candidates. Calcitonin exerts calcium-lowering effects both through its direct inhibitory effect on osteoclastic bone resorption and prevention of calcium reabsorption from renal tubulus. Among the anticalcemic agents available, calcitonin has the most rapid onset of action; the hypocalcemic effects appear within a few hours after administration. But continued usage diminishes its effect which is called the "escape phenomenon". The usual dosage of calcitonin is 80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for malignant hypercalcemia, even in the case of solid cancer such as lung cancer, though the mechanism is not clear. In lymphocytic proliferative disorders, a direct inhibitory effect on the proliferation of malignant cells accounts for the calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used for initial several days and glucocorticoid (30-40 mg/day) is continued along with calcitonin from the beginning of the treatment. Most effective and safe hypocalcemic agents for malignant hypercalcemia are the newly developed bisphosphonate compounds, which are not yet available in Japan. These agents interact chemically with hydroxyapatite on the bone surface and prevent osteoclastic function and activity. According to the data of our own investigation, pamidronate, one of the relatively new generation of bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia due to various kinds of malignancy by one intravenous administration (30-60 mg) without any adverse effect. In near future, the combination of calcitonin and bisphosphonates will also be the most effective medical management for malignant hypercalcemia in Japan.

Aged↗

Measurement of urinary fibrin/fibrinogen degradation products by latex photometric immunoassay.

Intraglomerular coagulation and fibrinolysis could be involved in the exacerbation of renal diseases, and urinary fibrin/fibrinogen degradation products (FDP) may be applicable as an index. Although the urinary FDP can be estimated by the latex agglutination method, this technique has disadvantages such as a poor sensitivity and is of the semiassay type. Recently, a new method of measurement which improves on these disadvantages, termed the latex photometric immunoassay (LPIA) method, has been developed. However, since FDP measurement by LPIA was designed for the purpose of serum FDP estimation, a measurement technique for urinary FDP has not yet been established. The purpose of the present study was to devise a measurement procedure for urinary FDP employing the LPIA method, and to obtain data on the normal levels of urinary FDP in healthy subjects. The results obtained may be summarized as follows. (1) The urinary pH and coexistent substances such as bovine serum albumin, glucose, urea, bilirubin, ascorbic acid, and hemoglobin, did not influence the urinary FDP measurement. (2) No changes in urinary FDP were observed after 28-day storage at -20 degrees C or -80 degrees C in the presence or absence of tranexamic acid. (3) The coefficient of variation was 5.3%. (4) The normal level of FDP excretion was 3.33 +/- 7.95 micrograms/day. The present data demonstrated that the LPIA method enables the urinary FDP to be measured quantitatively with a good sensitivity.

Fibrin Fibrinogen Degradation Products↗

Clinical significance of urinary fibrin/fibrinogen degradation products (FDP) as measured by latex photometric immunoassay in renal diseases.

It is possible that abnormalities of intraglomerular coagulation and fibrinolysis are involved in the exacerbation of kidney diseases. Urinary fibrin/fibrinogen degradation products (FDP) are regarded as an index of the intraglomerular coagulation and fibrinolysis. Although the conventional latex agglutination method for detecting urinary FDP has disadvantages such as a poor sensitivity and is of the semiassay type, latex photometric immunoassay (LPIA), a recently developed technique, is an assay with a high sensitivity. The present study was undertaken in an attempt to clarify the significance of urinary FDP as measured by latex photometric immunoassay in renal diseases. The subjects comprised were 60 patients with 15 kinds of renal diseases. Occasional urine samples and blood samples withdrawn at the time of urinary collection were examined. The FDP and FDP-E fractions (FDP-E) were measured by LPIA, and the FDP-D fraction (FDP-D) and fibrinopeptide A (FPA) were measured by enzyme immunoassay. The highest level of urinary FDP was seen in cases with diabetic nephropathy, followed by renal amyloidosis and chronic glomerulonephritis. While no correlation was noted between the urinary FDP levels and blood FDP levels, positive correlations were observed among the urinary protein, urinary FDP-E, FDP-D and FPA. The urinary FDP also revealed an inverse correlation with the l/serum creatinine. All cases with high levels of urinary FDP displayed renal dysfunction. These findings suggest that quantitative assay of the urinary FDP using LPIA is important for determining the degree of abnormality of intraglomerular coagulation and fibrinolysis in renal diseases.

Blood Coagulation↗

Role of intrarenal coagulation and anticoagulant therapy in the progression of diabetic nephropathy.

The aim of the present study was to clarify the role of intrarenal coagulation in the progression of renal dysfunction and to assess the efficacy of anticoagulant therapy in diabetic nephropathy patients. Forty-one diabetic patients were divided into 2 groups: group 1 (G-1), 20 patients with nephropathy; and group 2 (G-2), 21 patients without nephropathy. The levels of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta 15-42), fibrin/fibrinogen degradation products-D dimer (FDP-D dimer), and FDP-E products (FDP-E) and FDP, which are sensitive parameters of coagulation and fibrinolysis, were measured by radioimmunoassay, enzyme immunoassay (EIA), and latex photometric immunoassay, respectively, in both the blood and urine. The levels of urinary FPA, FDP-D, FDP-E, and FDP were found to be much higher in G-1 than in G-2. Significant relations were observed among the urinary levels of these four parameters. The renal function in all cases with higher levels of urinary parameters was severely deteriorated. Following heparin administration to these patients, marked reductions of the urinary FPA, FDP-D, and FDP-E and improvement of nephrotic syndrome were observed. The present data suggest that in diabetic nephropathy: (1) intrarenal coagulation is likely to occur and to induce progression of renal dysfunction; and (2) heparin therapy could be effective in diabetic nephropathy when the patients are selected according to the above parameters of coagulation and fibrinolysis.

Adult↗

[Within-day and day-to-day variations of serum M-CSF levels in healthy volunteers].

We have investigated on within-day and day-to-day variations of serum M-CSF levels in healthy volunteers (ranges of age: 20-21 years old). M-CSF levels in serum were measured using enzyme-linked immunosorbent assay (ELISA). Serum M-CSF levels in early morning were 1.31 +/- 0.30 ng/ml (mean +/- SD, n = 10) in male volunteers, 1.50 +/- 0.13 ng/ml (n = 10) in female volunteers. No significant difference was observed between male and female volunteers in serum M-CSF levels. No significant within-day variations in serum M-CSF levels were also observed. Serum M-CSF levels in period of thirteen days in each individual person were almost constant (n = 5). The inverse correlation was observed between M-CSF levels and number of neutrophils. The correlation, however, was not observed between M-CSF levels and number of monocytes. The present results suggest that there are mechanisms in vivo which maintain serum M-CSF in a constant level in each individual person.

Adult↗

[Detection of granulocyte-macrophage colony-stimulating factor activity in the supernatant of the cultured leukemic cells of adult T-cell leukemia with eosinophilia].

An adult T-cell leukemia (ATL) accompanied with eosinophilia is described. A 75-year-old female was admitted to our hospital because of lymphadenopathy. Her leukocyte count was 73,300/microliters, with 35.5% abnormal lymphocytes and 19% eosinophils. A majority of lymphocytes expressed CD4+CD8-. Acute ATL was diagnosed, since anti-HTLV-1 antibody in her serum and monoclonal integration of HTLV-1 proviral DNA in her peripheral mononuclear cells were detected. She was treated with THP-adriamycin, cyclophosphamide (CPA), and vincristine (VCR). Abnormal lymphocyte and eosinophil counts decreased and there was improvement in the lymphadenopathy. However she then complained of lymphadenopathy again. Her leukocyte count rose to 76,300/microliters, with 89% abnormal lymphocytes. Combination therapy with CPA, VCR, and doxorubicin was started and there was a temporal regression in lymphadenopathy, but her lymphadenopathy recurred and she died. The activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected in the supernatant of the cultured ATL cells, although interleukin-3, interleukin-5, and GM-CSF activities were not detected in her serum. It seems likely that the secretion of GM-CSF by ATL cells are responsible for the eosinophilia.

Aged↗

[The effects of acute administration of cadmium chloride on renal hemodynamics in rats].

The decreases of glomerular filtration rate (GFR) and renal blood flow (RBF) after acute administration of cadmium have been reported. The recent studies about renal failure induced by heavy metals revealed that the decrease of glomerular ultrafiltration coefficient is an important contributing factor in the onset of acute renal failure and that the changes of renal hemodynamics are less prominent factors. To clarify whether the changes of renal hemodynamics contribute to the decrease of GFR caused by cadmium, we evaluated the changes of renal hemodynamics and inulin clearance after acute intravenous infusion of cadmium chloride in rats. Cadmium chloride was continuously infused at the rate of 3.0 mumol/kg/min into SD rats. Mean arterial pressure was significantly increased immediately after the infusion of cadmium and unchanged during the experiment. 20 minutes after the infusion of cadmium, inulin clearance was decreased by 70% of the control value but RBF and renal vascular resistance (RVR) were unchanged. Filtration fraction was significantly decreased. 30 minutes after the infusion of cadmium, inulin clearance was further decreased by 51% of the control value. At the period, significant decrease of RBF (72% of control value) and increase of RVR (156% of control value) were observed. Urinary excretion of sodium and the ratio of urinary sodium to urinary inulin excretion were unchanged until 20 minute and were significantly decreased 30 minutes after the infusion of cadmium. Urinary volume was not changed throughout the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Chiral separation of barbiturates and hydantoins by reversed-phase high-performance liquid chromatography using a 25 or 50 mm short ODS cartridge column via beta-cyclodextrin inclusion complexes.

A high-performance liquid chromatographic method on a 25 or 50 mm short ODS cartridge column has been developed for the resolution of the enantiomers of some optically active barbiturates and hydantoins in human serum. beta-Cyclodextrin was used in the mobile phase. This method also seems to be an easy and effective way to test whether beta-cyclodextrin would be a useful chiral discriminator for a particular racemate.

Barbiturates↗

Inhibitory effects of endothelin-3 on vasopressin release from rat supraoptic nucleus in vitro.

Endothelin (ET) is thought to be involved in the central regulation of body water metabolism. A recent perfusion study of rat hypothalamus showed that ET has a direct stimulatory action on arginine-vasopressin (AVP) release. This study was undertaken to investigate whether ET acts directly on AVP release for supraoptic nucleus (SON) neurons, using brain slices containing only the SON. It was demonstrated that ET inhibited the AVP release dose-dependently from 10(-11) M to 10(-6) M. No difference of the effects of ET-1 and ET-3 on AVP release was observed. These results suggest that ET directly inhibits SON neurons through the ETB receptor.

Animals↗

Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation.

We investigated the interactions between human erythropoietin (hEpo) and serum factor(s) on murine megakaryocyte (MK) colony formation. Serum-free cultures supported the growth of a large number of murine MK colonies in the presence of murine interleukin-3 (mIL-3). The addition of fetal calf serum (FCS) to mIL-3-containing cultures resulted in only a minimal increase in the number of murine MK colonies. In contrast, hEpo alone had no murine MK colony-stimulating activities in serum-free cultures. hEpo required the presence of FCS, murine serum, or human serum in cultures to promote murine MK colony growth and synergized with these sera to stimulate murine MK colony formation. Furthermore, sera from patients with aplastic anemia showed higher synergistic activities with hEpo than sera from hematologically normal persons (normal human serum). When normal human serum was fractionated by gel-filtration chromatography, two peaks with the synergistic activity were observed in the eluent. However, serum did not show any synergistic effects with hEpo on the growth of murine GM colonies or murine colony-forming unit-erythroid-derived colonies. Although human serum synergized with hEpo to stimulate murine MK colony formation, human cytokines such as IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) failed to induce murine MK colony formation in Epo-containing cultures. In cultures containing human IL-1 alpha + human IL-6 + hEpo as well as in cultures containing hEpo, human IL-3 and human GM-CSF failed to show stimulatory effects on murine MK colony formation. Moreover, the synergistic activity of human serum with hEpo could not be neutralized by antibodies such as antihuman IL-1 alpha, antihuman IL-3, antihuman IL-4, antihuman IL-6, antihuman G-CSF, and antihuman GM-CSF. Our data show that serum contains a growth factor(s) that synergizes with Epo to stimulate the proliferation and differentiation of MK precursors, and strongly suggest that this factor(s) is an unique growth factor(s) that is distinct from IL-1 alpha, IL-3, IL-4, IL-6, G-CSF, and GM-CSF.

Anemia, Aplastic↗

Dihydrotestosterone accumulation in genital skin fibroblasts derived from elderly men with prostatic hyperplasia.

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-Androstane-3 alpha,17 beta-diol (3 alpha-diol) by 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 15 prepubertal boys (2-10 yr), 17 young men (20-40 yr), 13 elderly men (60-78 yr) without clinically evident prostatic pathology, and 17 elderly men (61-88 yr) with benign prostatic hyperplasia (BPH). Respective DHT formations from testosterone (5 alpha-reduction) and 3 alpha-diol (3 alpha-HSOR oxidation) were not different among genital skin fibroblasts of the 4 groups. However, DHT degradation to 3 alpha-diol (3 alpha-HSOR reduction) was significantly lower in fibroblasts from elderly men with BPH than in those from the prepubertal boys (P less than 0.01), the young men (P less than 0.01), and the elderly men without BPH (P less than 0.05). 3 beta-HSOR reduction in fibroblasts of the BPH group was significantly lower (P less than 0.05) than in those of the elderly men without BPH; however, it did not differ from values for the prepubertal boys and the young men. (3 alpha + 3 beta)-HSOR reduction was also significantly lower (P less than 0.05) in the BPH group than respective values of the three other groups. These results indicate that DHT accumulation may occur in genital skin fibroblasts from elderly men with BPH, resulting from a shift in the overall balance of androgen metabolism, which favors the net formation of DHT.

Aged↗

A kindred of multiple endocrine neoplasia type 2B.

We describe familial cases of multiple endocrine neoplasia (MEN) 2B: A 48-year-old man is the proband. He had pheochromocytoma, medullary thyroid carcinomas (MTCs), parathyroid hyperplasia, mucosal neuromas, eversion of eyelids and Marfanoid appearance, and then underwent adrenalectomy and total thyroidectomy. Family screening revealed that his two daughters (10 and 8 years old) had mucosal neuromas and increased serum calcitonin (CT). Both of them had MTCs but no pheochromocytoma, and their MTCs were surgically removed. The father and his children have been in favorable condition since the operations. Southern blot analysis with 33 polymorphic DNA probes was done in MTCs obtained from two daughters. An RBP3 (10q11.2) locus linked to a predisposing gene on chromosome 10 was uninformative in either patient because of constitutional homozygosity. Loss of heterozygosity at the MYCL1 locus on chromosome 1p32 was observed in MTC from the younger sister, but no loss of heterozygosity was recognized in other loci examined. Deletion of the 1p32 locus may play a role in the development of MEN 2B.

Adrenal Gland Neoplasms↗

Siblings of 21-hydroxylase deficiency (non-salt-losing) with aldosterone hypersecretion.

We describe siblings with the non-salt-losing form of 21-hydroxylase deficiency who had hypersecretion of aldosterone and plasma renin activity (PRA). Blood pressure and serum electrolytes in both cases were normal despite the aldosterone hypersecretion. Aldosterone secretion was elevated markedly with ACTH administration and with sodium deprivation and/or volume depletion during ACTH suppression by dexamethasone. With suppression by dexamethasone, aldosterone hypersecretion was decreased with lowering of the steroids proximal to the block in the biosynthetic pathway. However, urinary sodium excretion was decreased. These results suggest that the biosynthetic pathway for aldosterone production was preserved. Furthermore, aldosterone hypersecretion and high PRA may serve to compensate for the sodium loss which results in turn from the overproduction of the sodium-losing steroids, such as progesterone and 17 alpha-hydroxyprogesterone which are aldosterone antagonists.

Adolescent↗

Immunosuppressive factor produced by a B cell line derived from an adult T cell leukemia patient.

The immunosuppressive activity of culture supernatants from human T cell leukemia virus type I (HTLV-I)-infected cell lines was examined in vitro. Culture supernatants of both a HTLV-I-infected B cell line, IWS, established from an adult T cell leukemia (ATL) patient and a T cell line, MT-2, suppressed lymphocyte proliferative responses to stimulation with the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The immunosuppressive factor was not cytotoxic for lymphocytes and did not inhibit the spontaneous growth of ATL cells. It inhibited interleukin-2 (IL-2) production by PHA-stimulated T cells and it arrested PHA-stimulated T cells at the G0/G1 phase of the cell cycle and inhibited entry into the S phase. Furthermore, the factor significantly inhibited the expression of CD3, CD4, and IL-2 receptor (IL-2R) alpha-chain (CD25) on PHA-stimulated T cells. These results suggest that the immunosuppressive factors produced by HTLV-I-infected cell lines might function in the regulation of normal lymphocyte proliferative responses, and that they could play some role in the induction of the immunodeficient condition observed in ATL patients.

Adult↗

[Clinical significance of rheumatoid factor--its complement activating property and isotype].

We investigated the relationship between complement-activating properties of rheumatoid factors (RF) and their isotypes. Active and inactive RA patients without extra-articular symptoms (EAS) and those with EAS were studied. Patients with SLE, liver cirrhosis (LC) and normal volunteers were served as controls. Isotype of RF was measured by ELISA and complement activation (CA) of RF was measured by hemolytic assay. The CA values were significantly higher in RA patients with EAS than those in RA patients without EAS and with other diseases. The IgG and IgM-RF values were significantly higher in active RA without EAS than in inactive RA. Positive correlations between IgM-RF values and CA values were observed in RA with or without EAS, SLE and LC. The Sephadex G-200 gel filtration analysis of sera revealed CA in only 19S IgM fraction. Additionally, we purified 19S IgM-RF from sera of RA, SLE and LC patients by affinity chromatography, and found 19S IgM-RF had CA. These data suggest that serum IgM-RF may play a critical role in the pathogenesis of RA, especially in RA with EAS.

Arthritis, Rheumatoid↗