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Biomedical subjects

J Sato

Publications and source records attributed to J Sato.

At least 199 records · Page 11Linked to original sources

[Management of impaired glucose tolerance: physical training therapy].

Many epidemiological surveys have shown that impaired glucose tolerance (IGT) is at an increased risk of developing non-insulin-dependent diabetes mellitus (NIDDM). Other studies have reported that physical activity has been associated inversely with the prevalence of IGT and NIDDM, and that persons with high physical activity have a low incidence of NIDDM. These data suggest that physical training is an essential and effective therapy for IGT as a promising approach to the primary prevention of NIDDM. Moderately vigorous (about 50% of VO2 max) aerobic exercise that uses systemic skeletal muscles, such as walking, jogging, cycling, and swimming, at least three days a week, with each session lasting 30 min, are recommendable as the physical training prescription for IGT.

Diabetes Mellitus, Type 2↗

[Allelic chromosomal deletion using microsatellite polymorphism--the clue to the positional cloning of the tumor suppressor genes responsible for gastric carcinoma].

Cancers are caused by an accumulation of multiple genetic lesions that we are now beginning to understand. Gastric cancer has a different morphological appearance, ability to invade or metastasize, and response to treatment. The pattern of loss of heterozygosity is similar, but not necessarily the same among the different pathological lesions. It is likely that several unknown tumor suppressor genes could be participate in tumor behavior. Positional cloning using microsatellite genes would facilitate the identification of such additional tumor suppressor genes in the genome.

Alleles↗

Synergistic growth stimulation of mouse fibroblasts by tumor-derived adhesion factor with insulin-like growth factors and insulin.

Tumor-derived adhesion factor (TAF) has been purified as a major secretory protein with cell-adhesion activity from culture medium conditioned by human bladder carcinoma cells (K. Akaogi et al., Biochem. Biophys. Res. Commun., 198: 1046-1053, 1994). TAF is closely related or identical to a putative protein encoded by the mac25 gene (M. Murphy et al., Cell Growth & Differ., 4: 715-722, 1993) and prostacyclin-stimulating factor (T. Yamauchi et al., Biochem. J., 303: 591-598, 1994). TAF has a characteristic cysteine cluster in its NH2-terminal sequence, which is conserved in the NH2 termini of insulin-like growth factor-binding proteins. In the present study, we examined the interaction of TAF with insulin-like growth factors (IGFs) and insulin. Although in a ligand blotting assay TAF bound neither IGFs nor insulin, immunoprecipitation assay showed weak interaction of TAF with IGF-I, IGF-II, and insulin. TAF by itself stimulated the growth of BALB/c3T3 cells on the usual plastic substrates and significantly enhanced IGF- or insulin-mediated cell growth. Moreover, marked potentiation of the mitogenic activities of IGFs and insulin by TAF was found in the culture on type IV collagen substrates. The synergistic growth stimulation was completely blocked by heparin. These results suggest that TAF may regulate the growth of fibroblastic cells in collaboration with IGFs and insulin.

3T3 Cells↗

[Follicular bronchiolitis associated with rheumatoid arthritis].

A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40 mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickening of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.

Anti-Inflammatory Agents↗

[A case of prostate cancer diagnosed one and half year after retropubic prostatectomy for benign prostatic hypertrophy].

A 77-year-old male patient underwent retropubic prostatectomy for benign prostatic hypertrophy. Fourteen months after operation, a hard nodule was palpated on the left lobe on digital examination. Transrectal needle biopsy was performed, and the pathological diagnosis was poorly differentiated adenocarcinoma of the prostate. It was one and half year after prostatectomy that we diagnosed prostate cancer (stage D2).

Adenocarcinoma↗

Targeting cancer micrometastases with monoclonal antibodies: a binding-site barrier.

Monoclonal antibodies penetrate bulky tumors poorly after intravenous administration, in part because of specific binding to the target antigen. Experiments presented here demonstrate an analogous phenomenon in micrometastases; poor antibody penetration, attributable to a "binding-site barrier" phenomenon, can be seen in guinea pig micrometastases as small as 300 microns in diameter. Increasing the dose of antibody can partially overcome this limitation, but at a cost in specificity.

Animals↗

Collection and transplantation of peripheral blood stem cells in very small children weighting 20 kg or less.

The safety and efficacy of harvesting peripheral blood hematopoietic stem cells (PBSC) were evaluated in 38 children weighing 20 kg or less, with the smallest patient weighing 7 kg. The patients had a median age of 42 months and included 26 children with acute leukemias or lymphoma and 12 with various solid tumors. A total of 81 aphereses were performed, mostly in the recovery phase of chemotherapy, with or without granulocyte colony-stimulating factor, using a CS-3000 cell separator and regular procedure no. 3. Blood was withdrawn at a mean rate of 30 mL/min (range, 17 to 46 mL/min) through a temporary radial arterial catheter (20 to 24 guage) and returned through a larger catheter in a peripheral vein. Morbidity related to PBSC harvest was low and all aphereses were completed within 3 hours. The volume of blood per kilogram processed for each apheresis ranged from 85 to 615 mL (median, 270 mL). The median number of colony-forming units--granulocyte-macrophage (CFU-GM) and CD34+ cells collected were, respectively, 34 x 10(4)/kg and 15 x 10(6)/kg per apheresis and 126 x 10(4)/kg and 31 x 10(6)/kg per patient. Thirty-three patients (87%) required only a single apheresis to collect the minimum requirement of 10 x 10(4) CFU-GM/kg, including 28 patients (74%) from whom 30 x 10(4) CFU-GM/kg was obtained in a single apheresis. Twenty-three of the patients subsequently underwent autografts with PBSC. The median number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were, respectively, 10 (range, 6 to 15) and 14 (range, 9 to 46). The patients remained dependent on platelet transfusion support for a median of 10 days (range, 5 to 35). Thus, harvesting PBSC in very small children with active cancers is effective and safe and does not involve the risk of anesthesia or multiple invasive marrow aspirations.

Antineoplastic Combined Chemotherapy Protocols↗

Atomic absorption spectrometric determination of cadmium and lead in human and artificial teeth by direct atomization technique.

A method of graphite furnace atomic absorption spectrometry (GFAAS) with a direct atomization technique has been developed for the determination of trace amounts of Cd and Pb in human teeth and artificial teeth. The samples were ground to a particle size of less than 10 microns and mixed with the same amount of graphite powder. One-half to 2 mg of mixed sample was weighed in a tared graphite cup and atomized in a cup-type graphite furnace according to the heating program that was established. Absorbances were determined by integration of the spectral lines in the absorbance vs time spectrum. Calibration was affected using aqueous standard solutions. The results for six human tooth samples and two artificial tooth samples were in good agreement with the values obtained by GFAAS for dissolved samples. The relative standard deviations were 3.1-12% (n = 10) for Cd (19-95 ng g-3) and 0.9-8.1% (n = 10) for Pb (1.43-6.32 micrograms g-3). The determination limits corresponding to twice the standard deviation (sigma, n = 10) for blank measurements were 13 pg for Cd and 53 pg for Pb.

Cadmium↗

Optimal growth of human blood hematopoietic progenitor cells collected by apheresis for autografts.

For safe autografts with peripheral blood hematopoietic cells (PBSCT), better methods for determining the kinetics of stem cell populations and predicting engraftment speed after PBSCT need to be established. Current methods include culture in semi-solid medium and measurement of CD34 cell surface antigen. In this study with only partially purified blood cells obtained from children with cancer in remission, we compared the effects of phytohemagglutinin-stimulated lymphocyte-conditioned medium (PHA-LCM) and recombinant human cytokines on the growth of progenitor cells in a methylcellulose culture system. Interleukin-3 (IL-3) alone supported more progenitor growth than standard PHA-LCM by a factor of 1.54 for colony-forming unit granulocyte/macrophages (CFU-GM) and by a factor of 1.84 for burst-forming unit/erythroids (BFU-E). No significant change, in terms of the number of growing colonies, was observed by adding granulocyte/macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), or IL-1 to IL-3. However, the addition of G-CSF resulted in increased colony size. A further increase in CFU-GM growth was observed by the addition of IFN-gamma to the combination of cytokines. No significant effect was observed when stem cell factor (SCF) was added to the combination of cytokines containing IL-3, G-CSF, and IFN-gamma. This analysis suggests that the combination of IL-3, G-CSF, and IFN-gamma may provide sufficient stimulation for the growth of human blood cells. The effects of different oxygen tensions on progenitor growth in the presence of IL-3, G-CSF, and IFN-gamma were also evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Synergism of interleukin 12, interleukin 3 and serum factor on primitive human hematopoietic progenitor cells.

Interleukin 12 (IL-12), or natural killer cell stimulatory factor (NKSF), has multiple biologic effects on T lymphocytes and natural killer cells. In this study, we evaluated the effect of IL-12 on human hematopoiesis by analyzing the growth of CD34+33- cells in methylcellulose culture with or without serum. Blood cells were collected by apheresis from an expanded stem cell pool during the rebound phase of hematopoiesis after chemotherapy and purified by combined purification procedures to yield target CD34+33- cells. IL-12, by itself or in combination with IL-3 and erythropoietin (Epo), had no effect on the formation of colonies from the unfractionated blood mononuclear cells. In the presence of fetal bovine serum (FBS), IL-12 increased the number of colony forming units for granulocyte-macrophage (CFU-GM) from CD34+33- cells which responded to IL-3, but not the number of CFU-GM from those which responded to stem cell factor (SCF) or granulocyte colony stimulating factor (G-CSF). This effect was not abolished by the addition of monoclonal antibodies against tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 alpha, IL-6, G-CSF, or granulocyte/macrophage CSF (GM-CSF). However, the stimulatory effect of IL-12 was abolished in secondary plating in serum-containing methylcellulose culture after short-term (48 h) liquid incubation with IL-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Quantitative and qualitative comparative analysis of gradient-separated hematopoietic cells from cord blood and chemotherapy-mobilized peripheral blood.

Some of the uncertainty regarding the use of cord blood (CB) in transplant settings includes the suspected relative rarity of hematopoietic stem cells (SC) in CB and the feasibility of incorporating a cell separation protocol to remove red blood cells, which may result in an unacceptable loss of SC. To address this uncertainty, we isolated a SC fraction by Percoll or Ficoll gradients from CB and peripheral blood (PB), which had been mobilized by chemotherapy. The frequencies of mononuclear cells (MNC), CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and the output of colony-forming cells (CFC) after five weeks in long-term culture (LTC) assay were then evaluated. The mean numbers of these cells per ml of CB sample before gradient separation were, respectively, 4.9 x 10(6), 13.8 x 10(4), 3.0 x 10(3) and 681 (n = 37). In the recovery phase of PB, these numbers were, respectively, 2.0 x 10(6), 14.9 x 10(4), 3.5 x 10(3) and 270 per ml of processed blood at apheresis (n = 35). After Percoll separation, the recovery rates of these cells were, respectively, 29%, 92%, 97% and 95% in CB, and 65%, 87%, 123% and 102% in PB. After Ficoll separation of CB, the rates were, respectively, 55%, 107%, 92% and 105%. These results suggest that CB contains an adequate number of more immature progenitors which can be retained after cell separation with Percoll or Ficoll, thereby making it feasible to incorporate a cell processing procedure into a CB transplant protocol. Percoll separation provided a greater enrichment of cells than Ficoll.

Adolescent↗

The human interleukin-10 receptor gene maps to chromosome 11q23.3.

The human interleukin-10 receptor (IL-10R) gene has previously been mapped to chromosome 11. Here, we have determined the precise location of the human IL-10R gene by the fluorescence in situ hybridization method, and have found that the IL-10R gene maps to chromosome 11q23.3.

Chromosome Mapping↗

Low-dose halothane produces airway dilatation but does not alter parenchymal mechanics in the normal canine lung.

The purpose of this study was to examine whether halothane reduces the contractile tone of the normal lung and to distinguish the effects of halothane on airways from those on lung tissue. We also tested whether a mathematical model was capable of quantitatively describing the mechanical changes in the lung produced by halothane. We measured lung impedence (ZL(omega) a complex function of real (lung resistance) and imaginary (reactance) parts) at low frequencies in dogs using a forced volume oscillation technique before and during 1 MAC halothane anaesthesia. Halothane produced small changes in ZL(omega). The lung resistance tended to decrease during halothane anaesthesia whereas the lung reactance did not show change. Using an alveolar capsule technique to separate the airways from the lung tissue components, these lung mechanical changes were induced mainly by alterations in lung tissue and not in the airways. Our mathematical model featured a single airway leading to an alveolar region surrounded by a viscoelastic lung tissue. In the model analysis, estimates of airway resistance and inertance decreased by the administration of halothane. In contrast, estimates of lung tissue elastance and resistance did not change during halothane anaesthesia. These modeling results were consistent with those obtained by direct alveolar pressure measurements. Our results suggest that a low concentration of halothane dilates the airways but does not alter the parenchymal mechanics in the normal lung, and that the model provides a quantitative tool to assess lung mechanics precisely, if respiratory signals are measured only at the true airway opening.

Airway Resistance↗

In vivo modification of GABAA receptor with a high dose of pyridoxal phosphate induces tonic-clonic convulsion in immature mice.

The biologic cofactor, pyridoxal-5'-phosphate (PLP), is responsible for tonic-clonic convulsion in immature mice. The mechanisms underlying such convulsive fits induced by administration of a single high dose of PLP were studied. The administration of PLP resulted in a 13% increase of PLP in the P2 fraction compared to control P2, and the calculated data suggested that membrane bound PLP increased over 31% (approximately 1 microM). The P2 fraction of administered mice was treated with [3H]NaBH4 and analyzed by SDS-polyacrylamide gel electrophoresis. The radioactivity was mainly incorporated into a 52 kDa protein which corresponded to a GABAA receptor subunit. The addition of PLP in vitro competitively inhibited [3H]GABA binding as well as [3H]flunitrazepam binding to synaptic membranes in a concentration-dependent manner, and 50% inhibition was achieved with 1 mM PLP. The results obtained in the present study demonstrate that PLP was rapidly permeable into the brain through the immature blood-brain barrier and then bound directly to GABAA receptor. It is probable that specific amino groups of lysine residues on the GABAA receptor react in vivo with PLP to form Schiff bases, and that the in vivo modification of the receptor produces a degeneration of GABAergic neurotransmission leading to the onset of a convulsive fit.

Animals↗

Microallelotyping defines the sequence and tempo of allelic losses at tumour suppressor gene loci during colorectal cancer progression.

Microallelotyping of many regions from individual colorectal tumours was used to determine the sequence and tempo of allelic loss on 5q, 17p and 18q during neoplastic progression. No allelic losses were found in normal tissues surrounding colorectal neoplasms, but losses occurred abruptly on 5q at the transition from normal colonic epithelium to the benign adenoma, and on 17p at the transition from adenoma to carcinoma, indicating an essential role for these losses in tumour progression. Allelic losses were uniform throughout extensively microdissected benign adenomas and carcinomas. However, substantial allelic heterogeneity was found in high-grade dysplasia, the transition lesion between adenoma and carcinoma. Thus, allelic losses on 5q and 17p are associated with abrupt waves of clonal neoplastic expansion, and high-grade dysplasia is characterized by a high degree of allelic heterogeneity.

Adenocarcinoma↗

Effect of daily voluntary running on in vivo insulin action in rat skeletal muscle and adipose tissue as determined by the microdialysis technique.

The effect of physical training on in vivo insulin-stimulated glucose utilization in relation to glycolysis (lactate formation) in rat peripheral tissues was investigated in 8 sedentary controls (SC) and 7 voluntary running rats (VR). We used a sequential euglycemic clamp procedure (insulin infusion rate; 6.0, 30.0 mU/kg.min) in combination with a microdialysis technique in M. quadriceps femoris, vastus lateralis, and inguinal adipose tissue. In the clamp study, glucose infusion rate (GIR) averaged over 45-75 min during the 6.0-mU/kg.min insulin infusion was significantly (p < 0.01) higher in VR (15.36 +/- 0.83 mg/kg.min, mean +/- SE) than in SC (10.41 +/- 0.88 mg/kg.min), and the lack of a significant difference in GIR between VR and SC was found during the 30.0-mU/kg.min insulin infusion. In these tissues, there was no significant difference in dialysate lactate levels between VR and SC in the basal state without insulin or glucose infusion, or at an insulin infusion rate of 30.0 mU/kg.min. However, dialysate lactate concentrations in muscle averaged over 45-75 min during the 6.0-mU/kg.min insulin clamp procedure in VR (8.51 +/- 0.71 mg/dl) were significantly (p < 0.05) higher than in SC (6.18 +/- 0.48 mg/dl). These results indicated that insulin action in skeletal muscle and adipose tissue could be evaluated in vivo by using the microdialysis technique, and that an increase in GIR in VR was, in part, explained by an increase in lactate formation in skeletal muscle.

Adipose Tissue↗

Different localization of ETA and ETB receptors in the hyperplastic vascular wall.

We investigated which subtypes of endothelin-1 (ET-1) receptors are involved in the pathogenesis of angioplasty-induced lesion formation in the rabbit carotid artery. Four weeks after removing endothelial cells (EC), we noted a marked intimal hyperplasia. The Bmax values for [125I]ET-1 and [125I]IRL1620 (an agonist for the ETB receptors) bindings were greater in the hyperplastic artery, without changes in Kd values. [125I]ET-1 binding was completely inhibited by unlabeled ET-1 and Ro 46-2005, a mixed-type antagonist for the ETA and ETB receptors, but partially by BQ123, a selective antagonist for ETA receptors, and IRL1620. The [125I]ET-1 binding sites not inhibited with BQ123 were significantly increased in the hyperplastic artery. The binding study suggested the presence of non-ETA/non-ETB receptors. The rank order of the increasing ratio in the density of receptors was ETB > putative non-ETA/non-ETB > total ET-1 receptors > ETA. The histochemical experiments with biotinylated ET-1 at lysine-9 side chain alone or in combination with unlabeled ET-1, BQ123, Ro 46-2005, or IRL1620, showed the ETA receptors to be localized mainly in the media, whereas the ETB receptors localized mainly in the neointima. These results suggest that the increased ET-1 receptors, especially ETB and/or putative non-ETA/non-ETB, are closely related to the occurrence of the intimal hyperplasia after endothelial removal.

Analysis of Variance↗