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Biomedical subjects

J Sato

Publications and source records attributed to J Sato.

At least 271 records · Page 15Linked to original sources
PubMed1993

Effects of adrenodemedullation on in vivo insulin-stimulated glucose utilization in relation to glycolysis in rat peripheral tissue.

The effect of adrenodemedullation (ADMX) on insulin action was examined in anesthetized rats by means of a three-step euglycemic clamp procedure (insulin infusion rate: 0, 6.0 and 30.0 mU.kgBW-1.min-1) combined with a microdialysis technique in skeletal muscle and adipose tissue. The dialysate lactate levels in the above tissues increased in parallel with the plasma lactate levels during the sequential euglycemic clamp. In the euglycemic clamp, the glucose infusion rate (GIR) was significantly (P < 0.01) higher in ADMX rats (13.41 +/- 0.82 mg.kgBW-1.min-1) than in SHAM rats (10.21 +/- 0.87 mg.kgBW-1.min-1) during the 6.0-mU.kgBW-1.min-1 insulin infusion, and the lack of a significant difference between ADMX and SHAM rats was observed during the 30-mU.kgBW-1.min-1 insulin infusion. In skeletal muscle, the concentration of lactate in dialysate was significantly higher in ADMX rats (9.29 +/- 1.01 mg/dl) than in SHAM rats (6.22 +/- 0.47 mg/dl) (P < 0.05) at an insulin infusion rate of 6.0mU.kgBW-1.min-1. In adipose tissue, no significant difference in dialysate lactate levels was found between ADMX and SHAM rats at any insulin infusion rate. These results suggest that 1) it is possible to determine insulin action in skeletal muscle and adipose tissue in vivo by using the microdialysis technique, that 2) ADMX appears to result in a significant increase in insulin sensitivity, and that 3) lactate formation increased in skeletal muscle, but not in adipose tissue.

Adipose Tissue↗
PubMed1993

Expression of ras-P21 and ras gene alteration in pleomorphic adenomas.

The expression of ras-P21 protein and gene alteration of the K-ras gene were examined in 12 cases of pleomorphic adenoma of the salivary gland. The tumor cells in all 12 cases were strongly stained for ras-P21 protein by the indirect immunoperoxidase method, suggesting the enhanced expression of ras-P21 protein in pleomorphic adenomas. Analysis of the PCR products for the K-ras gene by temperature-gradient gel electrophoresis (TGGE) revealed that gene alterations such as point mutations occurred in 4 out of 12 pleomorphic adenoma tissues examined.

Adenoma, Pleomorphic↗
PubMed1993

Effects of progenitor cell dose and preleukapheresis use of human recombinant granulocyte colony-stimulating factor on the recovery of hematopoiesis after blood stem cell autografting in children.

The effects of progenitor cell dose on the recovery kinetics of hematopoiesis were assessed in 34 children who underwent marrow-ablative chemotherapy with peripheral blood stem cell (PBSC) autografting. One patient was not engrafted, probably because of a low dose of reinfused cells. In 25 patients whose PBSCs were harvested after intensive chemotherapy without recombinant granulocyte colony-stimulating factor (rG-CSF), we found a significant correlation between the colony-forming unit for granulocyte-macrophage (CFU-GM) infused per kilogram of the patient's body weight and the time to achieve an absolute granulocyte count (AGC) of > 0.5 x 10(9)/L (r = -0.817, p < 0.001) or a platelet count of > 50 x 10(9)/L (r = -0.703, p < 0.001). No association was seen between the number of burst-forming units for erythroid (BFU-E) infused and the speed of hematopoietic recovery. In the other 8 patients with low progenitor yields (< 1 x 10(5) CFU-GM/kg), in vivo induction of PBSC was attempted by administering rG-CSF (250 to 1000 micrograms/m2/day). Seven-day administration of rG-CSF before each leukapheresis increased the committed (CFU-GM: 37.7-fold; BFU-E: 45.6-fold) as well as multipotent (CFU-mix: 6.8-fold) progenitors. These collected cells were cryopreserved and then reinfused. Using a model for simulating hematopoietic recovery kinetics, we suggest that cells induced by rG-CSF could speed the recovery of granulocyte or platelet counts after PBSC autografting.

Adolescent↗
PubMed1993

[Significance of urinary fibrin/fibrinogen degradation products (FDP) measured by highly sensitive ELISA method in various renal diseases].

In order to clarify the abnormalities of intra-glomerular coagulation and fibrinolysis in patients with various renal diseases, urinary fibrin/fibrinogen degradation products (FDP) have been examined by several methods. We established a highly sensitive new method of enzyme-linked immunosorbent assay for urinary FDP. The results were as follow: 1) The mean +/- SD of urinary FDP in normal subjects was 10.30 +/- 9.08ng/ml. 2) The urinary FDP levels in chronic glomerulonephritis, nephrotic syndrome and chronic renal failure patients were significantly higher than normal subjects, and the levels in SLE, Alport's syndrome patients were higher than normal subjects. 3) The urinary FDP levels were a little bit higher in the patients with proliferative glomerulonephritis than in chronic glomerulonephritis patients with minor lesion or membranous nephropathy. 4) There was significant correlation between urinary FDP and urinary protein in chronic glomerulonephritis, while there was no correlation in nephrotic syndrome. 5) There was no correlation between urinary FDP and intra-glomerular fibrin deposits examined by immunofluorescent study in chronic glomerulonephritis, while in nephrotic syndrome, there were high levels of urinary FDP in the positive fibrin deposits cases. These results suggested that the most of the part of excretion of the urinary FDP in chronic glomerulonephritis is associated with the filtration of blood FDP to urine through the glomerular basement membrane, while in the nephrotic syndrome cases the origin of urinary FDP is related to the filtration and/or the intra-glomerular coagulation abnormalities.

Adolescent↗
PubMed1993

[The cranial MRI in severe cerebral palsy: a comparative study with clinical data].

The magnetic resonance examination was performed in 38 patients with severe cerebral palsy (CP; 15 males and 23 females) who had both motor delay (unable to move anywhere) and mental retardation (I. Q or D. Q below 30). Neuroimaging findings were compared with the CP type, etiology, and grade of understanding of language. Cranial magnetic resonance imagings (MRI) in CP were divided into five types. Type 1 : nine predominantly showed cyst-liked ventricles and periventricular hyperintensity on T2-weighted imaging (PVH) and only scarred basal ganglia and thalamus were visible. All suffered from neonatal asphyxia and the clinical type was rigospastic tetraplegia (RST). Type 2: eleven predominantly showed PVH and hyperintensity on T2-weighted (HT2) in basal ganglia and thalamus. All suffered from neonatal asphyxia and the clinical type was RST or rigospastic diplegia. Type 3: five showed PVH and three had cortical atrophy. All suffered from neonatal asphyxia and the clinical type was spastic diplegia. Type 4: four predominantly showed HT 2 in putamen and thalamus. Three had cortical atrophy. All suffered from neonatal asphyxia. The clinical type was athetotic CP (ATH). Type 5: nine predominantly showed HT 2 in globus pallidus. Four had cortical atrophy and two had hippocampal atrophy. All suffered from neonatal jaundice and the clinical type was ATH. All patients who suffered from neonatal asphyxia and spastic CP had MRI in PVH. All patients who suffered from neonatal asphyxia and ATH showed HT 2 in putamen and thalamus. Almost patients who suffered neonatal jaundice and ATH showed HT 2 in globus pallidus. With athetotic CP, cases with atrophy of the cerebral cortex or/and hippocampus were lower grade of understanding of language than no atrophy of both. The result of studies of MRI are in agreement with neuropathological findings.

Adolescent↗
PubMed1993

Measurement of serum levels of macrophage colony-stimulating factor (M-CSF) in patients with uremia.

Serum levels of monokines, including macrophage colony-stimulating factor (M-CSF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta (IL-1 beta), were measured in patients with chronic renal failure in an attempt to clarify the kinetics of these cytokines in the course of renal anemia. M-CSF was the only monokine detectable in the serum from all patients as well as healthy donors, making this cytokine feasible and reliable for serial evaluations. On all occasions, the level of M-CSF in uremic patients was significantly higher than that in healthy donors (29.4 +/- 12.3 vs. 5.5 +/- 1.1 ng/mL). In patients undergoing hemodialysis, the serum level of M-CSF was greater than that in patients undergoing continuous ambulatory peritoneal dialysis or in uremic patients without dialysis therapy. No difference was observed, however, in the levels of IL-1 alpha, IL-1 beta and TNF-alpha levels in these groups. Patients with severe anemia were subsequently treated with 60 to 80 U/kg per week of human recombinant erythropoietin (rhEpo) for 3 months. After this replacement therapy, hemoglobin levels increased with a variable change ranging from 0 to 3.5 g/dL. The pretherapy M-CSF level, however, was found to predict statistically the response to the therapy (p < 0.05). Patients with a lower pretherapy value responded better to rhEpo therapy; those with a higher level showed a minor degree of response. From these results, we postulate that the elevated M-CSF serum level in uremic patients is in part a consequence of the dialysis procedure and that rhEpo therapy is more effective in patients who are under sophisticated dialysis protocol and have a lower M-CSF level.

Erythropoietin↗
PubMed1993

Effect of pleural effusion on respiratory mechanics, and the influence of deep inflation, in dogs.

We wished to study how pleural effusion affects dynamic mechanics of the lung and the chest wall. We also determined if these changes could be reversed by deep lung inflations. Pleural effusion was produced by saline infusion into the pleural space. During the infusion and over the following 2 hours, dynamic elastance and resistance of the lungs, the chest wall and the whole respiratory system were recorded. Dynamic elastance and resistance of the lung increased significantly during fluid loading and were partially, and only transiently, reversed by deep inflations. Dynamic elastance and resistance of the chest wall were little affected by these procedures. Thus, pleural effusion can have significant effects on dynamic elastance and resistance of the respiratory system (ERS, RRS). The transient nature of the change in lung parameters after deep inflation suggests that therapies based on periodic lung inflations may be of little benefit to patients with this condition.

Animals↗
PubMed1993

[Evaluation of the benefits of sodium 2-mercaptoethane sulfonate (MESNA) therapy for children undergoing high-dose chemotherapy].

Preventive effects of hemorrhagic cystitis by the use of sodium 2-mercaptoethane sulfonate (MESNA) was evaluated in 40 children undergoing peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy which included high-dose cyclophosphamide (CY, 50mg/kg x 2). Fifteen patients received MESNA (group A) and 25 did not (group B), and all received concomitant hyperhydration (3,000ml/m2/day). No renal dysfunction or toxicity attributed to the use of MESNA was observed in either group of patients. Transient hemorrhagic cystitis developed in one of the 15 group A (6.7%) and 3 of 25 (12.0%) group B patients but there was no statistical significance. Although the results may suggest that MESNA is a controversial agent in preventing hemorrhagic cystitis caused by CY when hyperhydration protocol is used, further observation with a larger number of patients is required to establish a firm conclusion.

Adolescent↗
PubMed1992

Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier.

Monoclonal antibodies (MAbs) often distribute nonuniformly in tumors. In part, that observation reflects intrinsic heterogeneity within the tumor; in part, it reflects poor penetration through tumor substance. Several years ago, we proposed the "binding site barrier" hypothesis (J.N. Weinstein, R.R. Eger, D.G. Covell, C.D.V. Black, J. Mulshine, J.A. Carrasquillo, S.M. Larson, and A.M. Keenan, Ann. NY Acad. Sci., 507: 199-210, 1987; K. Fujimori, D.C. Covell, J.E. Fletcher, and J.N. Weinstein, Cancer Res., 49: 5656-5663, 1989), the idea that antibodies (and other ligands) could be prevented from penetrating tumors by the very fact of their successful binding to target antigen. Calculations suggested that this might be a significant factor in the therapy of even microscopic nodules. The higher the affinity and the higher the antigen density, the greater the barrier. Here, we provide direct experimental evidence of such a barrier to the percolation of D3 MAb through intradermally implanted line 10 carcinoma of guinea pigs. After affinity purification using glutaraldehyde-fixed line 10 cells, the D3 had an average immunoreactivity of 88%, a binding constant of 1.6 +/- 0.3 (SEM) x 10(10) M-1, and saturation binding of 355,000 +/- 15,000 molecules/cell. Using a combination of double-label autoradiography and double-chromagen immunohistochemistry, we determined simultaneously the distribution of (a) i.v. injected D3 MAb; (b) coinjected isotype-matched control IgG (BL3); (c) D3 antigen; (d) blood vessels. The previously developed mathematical models aided in the design of these experiments. Double immunochemical staining of the tumors showed antigen-rich patches 100-800 microns across, surrounded by blood vessels. At a low MAb dose (30 micrograms), binding to antigen severely hindered penetration into antigenic patches as small as 200 microns, even at 72 h. Explanation of this finding by a physical barrier was ruled out by the observation that BL3 distributed uniformly in the same patches. At a higher dose (1000 micrograms), the binding site barrier could be partially overcome. The same general principles of micropharmacology may apply to biological ligands other than antibodies, including those secreted by genetically modified cells.

Adenoma, Bile Duct↗
PubMed1992

Quantification of 5-fluoro-2'-deoxyuridine in plasma by gas chromatography and negative-ion chemical ionization mass spectrometry.

A sensitive and specific method using gas chromatography and negative-ion chemical ionization mass spectrometry is described for the determination of 5-fluoro-2'-deoxyuridine (FdUrd) in plasma. The method is based on the formation of the pentafluoropropionyl derivative of FdUrd and of its stable isotope as internal standard after sample clean-up by solid-phase extraction and purification by high-performance liquid chromatography. Quantification in plasma was possible down to 300 pg/ml. The method was applied to the analysis of plasma levels of FdUrd in mice and dogs.

Animals↗
PubMed1992

Correcting for the Bernoulli effect in lateral pressure measurements.

Measurement of airway pressure is essential in the study of respiratory mechanics, and is usually done via a lateral tap in the conduit (e.g., endotracheal tube, cannula, or mouthpiece) leading into the subject's airway. Such pressure measurements, however, may be severely affected by the Bernoulli effect if the diameter of the conduit is small and the gas flow through it sufficiently high. We present in this note a simple method of assessing whether or not the Bernoulli effect is important in any particular situation. The technique involves comparing the pressure-flow relationships of the conduit obtained both by blowing air through it from one end and sucking air in the reverse direction by applying negative pressure at the same end. If the resistance of the conduit is the same for gas flow in both directions, then half the magnitude of the difference between the two pressure-flow relationships gives the magnitude of the Bernoulli effect pressure. We give results of an experimental situation in which this was the case. We also show that those conditions under which the Bernoulli effect is likely to be a problem are also those under which the velocity profile is likely to be approximately flat, thereby permitting the magnitude of the Bernoulli effect to be easily calculated.

Air Pressure↗
PubMed1992

Combination of recombinant cytokines fails to produce ex vivo expansion of human blood hematopoietic progenitor cells.

The concept of ex vivo expansion of the human progenitor cell population was tested in this study. In the presence of interleukin-3 and -6 we compared the abilities of various liquid culture conditions of human blood-derived hematopoietic progenitor cells to yield a suitable condition for the expansion of blood progenitor cells. Although the best result was obtained in the gastpermeable bag culture system, the enhancement effect (maximum of 3.8-fold for granulocyte/macrophage colony-forming units and 3.0-fold for erythroid burst-forming units) lasted for only a short period (less than 6 d). The results of this study are disappointing for clinical use, and attempts with currently available technology appear to be limited in their potential.

Adolescent↗
PubMed1992

Successful autograft with peripheral blood stem cells in a child with T-lymphoblastic leukemia.

Peripheral blood stem cells (PBSC) were collected by two leukaphereses and cryopreserved in a 3-year-old girl with T-lymphoblastic leukemia; this was after remission was induced by an investigative regimen when she failed to respond to a first-line induction therapy. The patient received marrow-ablative chemotherapy 4.5 months after the diagnosis; this was followed by the infusion of thawed PBSC (203 x 10(4) CFU-GM/kg). The peripheral granulocyte count reached 0.5 x 10(9)/L by day +7 and the platelet count reached 20 x 10(9)/L by day + 9. Thereafter, the leukocyte count increased to 38 x 10(9)/L by day +14, with a gradual decline to normal levels. She has remained in unmaintained, complete remission 47 months after the autograft, with full school activity. This case illustrates the PBSC autograft is useful as an alternative to bone-marrow transplantation in a selected patient population, and extends the application of cure-oriented therapy to refractory childhood leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Suspected distinct activation pathways of human lymphocytes induced by antilymphocyte globulin and anti-CD3 monoclonal antibody result in different secretion of hematopoietic colony-stimulating activities.

We evaluated the activation sequence of peripheral blood lymphocytes from healthy donors using different mitogens, including antilymphocyte globulin (ALG), anti-CD3 monoclonal antibody (OKT3), and phytohemagglutinin (PHA). Blood mononuclear cells stimulated by ALG, OKT3 and PHA incorporated 3H-thymidine in the same way. When enriched T cells were tested in the presence of interleukin-1 alpha (0 to 100 U/ml, incorporation of 3H-thymidine was greater in those cells stimulated by ALG than by PHA. OKT3 did not activate enriched T cells. Thymidine incorporation was reduced to less than 50% of maximum concentrations by the addition of 10(-7) mol/1,25-dihydroxyvitamin D3 (vit D3) in PHA- or OKT3-activated cells. However, the inhibitory effect of vit D3 was not apparent in ALG-activated cells. Production of granulocyte-macrophage colony-stimulating factor and interleukin-3 by lymphocytes upon activation was consistently higher when cells were treated with ALG or PHA than with OKT3. Taken together, the data indicate that there appear to be distinct functional mechanisms between ALG- and OKT3-induced lymphocyte activation that lead to characteristic immunohematologic events.

Antibodies, Monoclonal↗
PubMed1992

Factors affecting the accuracy of esophageal balloon measurement of pleural pressure in dogs.

Simultaneous measurement of esophageal and tracheal pressures during an occluded inspiratory effort was used to assess the accuracy of the esophageal balloon for measuring pleural pressure in dogs. Esophageal balloons were inserted in five mongrel dogs, and an occlusion test was performed with the balloon tip 5, 10, 15, 20, and 25 cm above the esophageal sphincter; at lung volumes of functional residual capacity (FRC) and FRC + 600 ml; and in supine and right- and left-side lying postures. The protocol was repeated in paralyzed animals. This time the occlusion test was performed by injecting air into a plethysmograph to change the body surface pressure, simulating pressure changes produced by respiratory efforts in spontaneously breathing animals. In 47% of the tests in spontaneously breathing dogs, the slope of esophageal vs. tracheal pressure varied greater than 10% from unity. After paralysis the slope did not vary greater than 5% from unity under any circumstance. These data indicate that the poorer performance of the occlusion test in nonparalyzed dogs is due to active tension in the walls of the esophagus and stress induced in the intrathoracic soft tissues by the descent of the diaphragm during a breathing effort.

Animals↗
PubMed1992

Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine.

We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction.

Administration, Inhalation↗
PubMed1992

Effects of daily physical activity on insulin action in the elderly.

The effects of daily physical activity on peripheral insulin action were investigated in aged individuals. Glucose infusion rates (GIR) during the euglycemic insulin clamp procedure in aged bedridden, aged controls, and aged athletes were compared with those in young controls and young athletes at insulin infusion rates of 40 and 400 mU.m-2.min-1 to estimate insulin action at physiological and maximal insulin concentrations, respectively. At both insulin infusion rates, GIR was significantly higher in aged athletes and significantly lower in aged bedridden subjects than in aged controls. Although there was no statistical difference in GIR at 400 mU.m-2 x min-1 between young athletes and young controls, GIR at 40 mU.m-2 x min-1 was higher in young athletes than in young controls. Comparison of the aged and young groups showed that although GIR at 400 mU.m-2 x min-1 was significantly lower in aged controls than in young controls, there was no significant difference between the aged athletes and the young athletes. We conclude that insulin responsiveness (insulin action at the postreceptor binding site) may decrease with the aging process and may be further affected by physical inactivity. Although physical training may improve insulin responsiveness in aged individuals up to levels similar to those in young athletes, physical training in young individuals may improve only insulin sensitivity.

Adult↗