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Biomedical subjects

K Asano

Publications and source records attributed to K Asano.

At least 343 records · Page 19Linked to original sources
PubMed1990

Chemical modification of erythropoietin: an increase in in vitro activity by guanidination.

Human recombinant erythropoietin (rHuEPO) was chemically modified with several group-specific reagents in order to study the role of each kind of amino-acid residue in its biological activity. Guanidination of the amino groups of the lysine residues yielded derivatives that showed higher activities in vitro than native rHuEPO, whereas amidination had no effect on the activity. By contrast, modification of the positive charges of the lysine residues to neutral or negative charges, such as in carbamylation, trinitrophenylation, acetylation or succinylation, caused a significant loss of rHuEPO activity. Chemical modification of other amino-acid residues, such as arginine and tyrosine residues or carboxyl groups, also led to loss of activity.

Arginine↗
PubMed1990

Cloning of an osteoblastic cell line involved in the formation of osteoclast-like cells.

Experiments have been carried out to determine the mechanisms involved in the formation of osteoclast-like cells from spleen cells in mice. Osteoclasts were defined as tartrate-resistant acid phosphatase-positive multinucleated cells (TRACP-positive MNCs) in which specific calcitonin receptors were identified by autoradiography with labeled salmon calcitonin. Furthermore, cultures rich in these cells produced resorption pits when grown on dentine slices. Several clonal cell lines were obtained from fetal mouse calvariae and screened for their ability to induce TRACP-positive MNCs in response to 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3] in co-cultures with spleen cells. A cell line, KS-4, was identified with the greatest potency in inducing osteoclast-like cell formation in co-culture with spleen cells. The capacity of KS-4 cells to produce this effect was much greater than that of two bone marrow-derived stromal cell lines (MC3T3-G2/PA6 and ST2 cells), which we have previously shown to be effective in this system but to require treatment with dexamethasone in addition to 1 alpha, 25(OH)2D3 (Udagawa et al.: Endocrinology 125:1805-1813, 1989). Parathyroid hormone (PTH) increased cAMP production in KS-4 cells, and PTH and interleukin-1 alpha also induced TRACP-positive MNCs in co-cultures with spleen cells. Contact between living KS-4 and spleen cells was necessary for osteoclast formation to take place, since this did not occur when the two populations were separated by a membrane filter, or when the KS-4 cells were killed by fixation. Separate cultures of either spleen cells or KS-4 cells formed no TRACP-positive MNCs. KS-4 cells synthesized predominantly type I collagen, formed bone nodules without added of beta-glycerophosphate in a long-term culture, and expressed increasing alkaline phosphatase activity after confluence in culture. These results indicate that the KS-4 cells have properties consistent with progression toward the osteoblast phenotype and represent a single cell line with the ability to promote osteoclast formation by a contact-requiring process.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats.

Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [14C, 3H]KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer.

Animals↗
PubMed1990

Effects of SO2 and pH on blood-gas partition coefficients of inert gases.

Potential effects of SO2 and of pH on blood-gas partition coefficients, lambda, for inert gases, including SF6, ethane, cyclopropane, halothane, diethyl ether, acetone and N2, were systematically investigated using human blood. Measurements on lambda were performed at 37 degrees C in conditions of varied SO2 and pH using gas chromatography. Incorporating the experimental data on lambda, multiple inert gas elimination was applied to 18 patients with varied chronic lung diseases, in order to estimate the effects of SO2 and of pH on both inert gas exchange and resultant recovery of VA/Q distribution in the lung. For this purpose, the data obtained by the procedure of multiple inert gas elimination were analyzed with the classical approach but allowance was made for lambda of the indicator gas to vary according to exchange of O2 and of CO2 in the pulmonary capillary. Among the gases studied, ethane, cyclopropane, halothane and diethyl ether showed significantly smaller lambda values in the oxygenated blood than in deoxygenated blood, whereas SF6, acetone and N2 were little dependent on SO2. An increase in lambda was found for ethane and a decrease for halothane with increasing pH in the blood. The other gases were not significantly influenced by pH. In spite of these experimental findings, regional difference of either SO2 or pH in the lung did not exert important influence on the inert gas exchange or on the predicted VA/Q distribution. In conclusion, blood-gas partition coefficients of some inert gases are consistently altered by SO2 and pH, but their possible effects on inert gas exchange seem to be negligible.

Adult↗
PubMed1990

Continuous distributions of ventilation and gas conductance to perfusion in the lungs.

Theoretical analysis and experimental observations were conducted to establish a method allowing to demonstrate the characteristics of distribution of ventilation (VA) as well as of diffusive conductance (G) to perfusion (Q) in the lungs. O2, CO2 and CO binding to hemoglobin molecules within the erythrocyte together with six inert gases including SF6, ethane, cyclopropane, halothane, diethyl ether and acetone, of varied solubility in blood and different diffusivity in lung tissue, were used as indicator gases. 15 patients with interstitial pneumonia of unknown etiology, placed in the supine position, were given a mixture of 21% O2 and 0.1% CO in N2 as the inspired gas and saline containing appropriate amount of the six inert gases was infused via an antecubital vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken through catheters inserted into the femoral and pulmonary artery. The concentrations of the indicator gases in the samples were measured by gas chromatography, with electrodes or with the Scholander gas analyzer. Assuming that the mass transfer efficiency of a given indicator gas at each gas exchange unit would be limited by VA/Q and G/Q ratios, the data obtained from the human subjects were analyzed in terms of a lung model having 20 units along the VA/Q and G/Q axes, respectively. The numerical analysis including the procedure of simultaneous Bohr integration for O2, CO2 and CO in a pulmonary capillary and the method of weighted least-squares combined with constrained optimization permitted the data to be transformed into a virtually continuous distribution of Q against VA/Q and G/Q axes. The numerical procedure was strictly tested using various artificial distributions of VA/Q and G/Q ratios, showing that it could characterize the distributions containing up to at least two modes on VA/Q-G/Q field with a substantial accuracy. Analytical results estimated from the patients with interstitial lung disease revealed the following features. (1) There appears to be bimodal distribution of Q along G/Q axis extending to relatively low G/Q less than 10(-3) ml(STPD)/(ml.Torr), which may limit O2 exchange between alveolar gas and capillary blood. This area of low G/Q receives 10% of total Q. (2) Severe diffusion limitation causing disequilibrium of the inert gas across the blood-gas barrier is solely observed in 2 out of 15 patients and an amount of Q associated with this phenomenon is very small (below 1%).(ABSTRACT TRUNCATED AT 400 WORDS)

Carbon Dioxide↗
PubMed1990

Evaluation of the microplate hybridization method for rapid identification of Legionella species.

Rapid genetic identification of 23 Legionella species was performed using microdilution plate hybridization. When an isolate appeared to be a strain of the Legionella species, its DNA was quickly extracted, labelled with photobiotin and distributed to microdilution wells where 23 different DNAs had previously been immobilized. After hybridization for 90 min at 45 degrees C, the microdilution well which emitted the maximum fluorescence was determined. The criterion for interpreting results of this genetic identification method is given.

DNA, Bacterial↗
PubMed1990

Formation of multicellular spheroids composed of adult rat hepatocytes in dishes with positively charged surfaces and under other nonadherent environments.

Adult rat hepatocytes formed floating multicellular spheroids in primary culture in an uncoated plastic dish with a positively charged surface. Cells in the spheroids formed in such a simple way were similar to those formed in dishes coated with proteoglycan fraction isolated from rat liver reticulin fibers; in both cases, cells maintained high ability to produce albumin and poor ability to proliferate in response to epidermal growth factor. Coating dishes with albumin was also helpful in spheroid formation; coating with 2-hydroxymethyl methacrylate resulted in formation of incomplete spheroids. Elimination of serum factors was essential for the formation of spheroids; when cells were washed with serum-containing medium before seeding or if the medium was replaced with a serum-containing medium, spheroid formation was completely inhibited. Collagens, fibronectin, and laminin, all of which promote the adhesion and spreading of hepatocytes on substrates, inhibited spheroid formation. Furthermore, collagens disintegrated spheroids, and cells in the monolayer initiated proliferation. Thus, two distinct, mutually exclusive features of primary culture of adult hepatocytes apparently exist; monolayer culture with proliferative activity in an adherent environment and spheroid culture with poor proliferative activity and high albumin-producing ability in a nonadherent environment.

Albumins↗
PubMed1990

Effects of intraarterial chemotherapy using the new lipophilic anticancer agent 'KM2210' (estradiol-chlorambucil) dissolved in lipiodol on Walker 256 carcinosarcoma in Wistar rats--a preliminary report.

The effect of a new oil-soluble anticancer agent 'KM2210' (estradiol-chlorambucil) dissolved in lipiodol (LPD) was investigated as intraarterial chemotherapy, using 40 Wistar rats bearing Walker 256 carcinosarcoma in the extremities. KM2210-LPD significantly inhibited tumor growth and prolonged the survival time, as compared to LPD alone or saline alone, p less than 0.01 and p less than 0.01, respectively. Pathological study revealed that KM2210-LPD made the tumor necrotic. It was revealed that KM2210-LPD injected into the femoral artery was retained in the hind limb tumor. These findings suggest that KM2210 may possibly become a new anticancer agent with potential clinical use in LPD chemoembolization.

Animals↗
PubMed1990

[Control of ventilation and aerobic work capacity in elite climbers].

Hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR), and maximal oxygen uptake (VO2max) were measured in elite male climbers (Clim.: n = 4) and physically active controls (Con.: n = 8). Although mean value of S, an index of HCVR, showed almost the same values in both groups (Clim.: 2.26 +/- 0.62 vs. Con.: 1.85 +/- 0.58 l.min-1.Torr-1), mean value of A, an index of HVR, was significantly higher in climbers than controls (Clim.: 237.8 +/- 109.2 vs. Con.: 111.3 +/- 62.0 l.min-1.Torr-1). Mean value of VO2max in climbers was not different from that in controls (Clim.: 49.3 +/- 2.9 vs. Con.: 47.5 +/- 5.7 ml.kg-1.min-1). These results demonstrate that elite climbers are characterized by their enhanced ventilatory response to hypoxia rather than prominency in aerobic work capacity. It is speculated that enhanced HVR in climbers makes compensation for decreased VO2max at high altitude. The enhanced HVR in elite climbers who have ordinary values in VO2max may be one of factors in their successful performance at extreme altitude.

Adult↗
PubMed1990

[A clinical study of the renal pelvis and ureteral cancer].

During the 13 years from 1976 to 1988, 160 patients with renal pelvic and ureteral cancer were reviewed based on a new general rule for clinical and pathological studies on renal pelvic and ureteral cancer of Japanese Urological Association. There were 71 renal pelvic cancers, 80 ureteral cancers, and 9 cancers in both regions. Patients ranged in age from 35 to 91 years old (average: 63). The involved side was right in 63 and left in 97. The most frequent symptom was hematuria, which was seen in 81.1%. IVP revealed the findings of filling defects, hydronephrosis, and non-visualized kidney in 99.7% of the patients. Total nephroureterectomy with bladder cuff resection was performed in 123 cases, nephroureterectomy in 16 cases, nephrectomy in 5 cases, partial ureterectomy in 10 case, and biopsy in 6 cases. As adjuvant therapies, irradiation was performed in 32 and chemotherapy in 123. Histologically, 156 were with transitional cell carcinoma, one squamous cell carcinoma, one adenocarcinoma and 2 unclear, the over-all survival rate of this study at 1, 3, 5 and 10 years were 86.8%, 73.0%, 65.3% and 45.6%, respectively. No patient with lymph-node metastasis (N+) survived longer than 5 years. All patients with M(1) died within one year. There were no difference of prognosis between renal pelvic cancer and ureteral cancer. Regarding various prognostic factors, our series gave the same results as previous reports. However, it should be stressed that pathological grading was the most important prognostic factor.

Adult↗
PubMed1990

Effects of proxigermanium on interferon production and 2',5'-oligoadenylate synthetase activity in the lung of influenza virus-infected mice and in virus-infected human peripheral blood mononuclear cell cultures.

Proxigermanium (SK-818) is a synthesized organic germanium compound having various biological activities. The effects of proxigermanium on interferon (IFN) production in mice infected with influenza virus and virus-infected human peripheral blood mononuclear cells (hPBMC) were investigated. Proxigermanium alone did not induce IFN production in normal mice or in hPBMC without viral infection. On the other hand, proxigermanium enhanced alpha/beta IFN production in viral-infected mice and hPBMC. Since proxigermanium is known to have antiviral activity in vivo but not in vitro, it is likely that the IFN production augumenting activity of proxigermanium is involved in its antiviral activities.

2',5'-Oligoadenylate Synthetase↗
PubMed1990

Mono-sulfated glycosphingolipids of human amnion.

Two mono-sulfated glycosphingolipids were isolated from the human amnion. By carbohydrate analysis and acid hydrolysis, the structure of these glycolipids are proposed to be galactosylsulfatide (SM4s) and lactosylsulfatide (SM3). The major fatty acids of SM4s and SM3 were C16:0. The yields of SM4s and SM3 from the amnion were about 340 and 110 pmol/g wet wt, respectively.

Amnion↗
PubMed1990

A case of GM1-gangliosidosis type I: glycosphingolipid profiles of urine and transformed lymphocytes and beta-D-galactosidase activities in peripheral lymphocytes, cultured skin fibroblasts and transformed lymphocytes.

A female infant with early-onset GM1-gangliosidosis type I was investigated. The lymphocytes, transformed lymphocytes and cultured skin fibroblasts of the patient were demonstrated to have severe beta-D-galactosidase deficiency. The beta-D-galactosidase activities of these cells from the patient's father and mother were at the lower limit of the normal range. The oligosaccharide accumulation in urine of the patient showed the typical type I GM1-gangliosidosis pattern, but no GM1 ganglioside was detected in the patient's urine or transformed lymphocytes. The clinical features were compatible with infantile GM1-gangliosidosis. The mixture of homogenates from the cultured fibroblasts or transformed lymphocytes of the patient and controls showed no complementation of beta-D-galactosidase activity against the controls.

Cells, Cultured↗
PubMed1990

[A clinical and pathological study of small renal cell carcinomas].

Ten cases of a small renal cell carcinoma having a tumor that was 3 cm or less have been studied both clinically and pathologically. In nine of the 10 cases, the tumor had been detected incidentally, and all 9 were asymptomatic. Renal lesion were diagnosed all of the 10 cases by computed tomography and in 9 cases by ultrasonography. The pathological characteristics of small renal cell carcinoma are characterized by an expansive development, an alveolar structure, a clear cell subtype, a low grade nuclear atypism, and a general lack of infiltration. The postoperative follow up period was 20 months on average, and all patients had survived with no appearance of a new lesion.

Adult↗
PubMed1990

[Characteristics of impaired gas exchange in patients with chronic obstructive pulmonary disease].

Eleven patients with chronic obstructive pulmonary disease (COPD), placed in a supine position, were given a mixture of 0.1% CO and 21% O2 in N2 as inspired gas and normal saline containing the six inert gases including SF6, ethane, cyclopropane, halothane, diethyl ether and acetone via the antecubital vein. After the steady state was established, the expired gas was collected and both arterial and mixed venous blood were simultaneously sampled through the catheter inserted either into the femoral or pulmonary artery. Assuming that mass transfer efficiency of a given indicator gas at each gas exchange unit would be limited by the ratio of ventilation to perfusion (VA/Q) and by that of diffusive conductance to perfusion (G/Q), the data were analyzed by means of a lung model with 20 units along the VA/Q and G/Q axes, respectively. By application of the method of weighted least-squares combined with the idea of constrained optimization, the data were transformed into a virtually continuous distribution of Q against VA/Q and G/Q axes. Analytical results revealed that: 1) patients with advanced COPD show widening of VA/Q distribution accompanied with a significant contribution of either high VA/Q (emphysematous change) or low VA/Q area (peripheral airway involvement). and 2) their Q distributions along the G/Q axis are unimodal but have an area with a relatively low G/Q, indicating a small but appreciable contribution of diffusion limitation to their hypoxemia. In conclusion, the findings consistently suggest that inhomogeneity of G/Q may partly be responsible for the impaired gas exchange in the cases of COPD.

Humans↗
PubMed1989

Continued high albumin production by multicellular spheroids of adult rat hepatocytes formed in the presence of liver-derived proteoglycans.

Adult rat hepatocytes formed floating multicellular spheroids, when they were cultured with proteoglycan fraction isolated from rat liver reticulin fibers. Cells in the spheroid showed only low growth activity. Albumin production by the spheroids increased up to 1.5 micrograms/micrograms DNA/day (180 micrograms/mg Protein/day) during the first 6 days and remained constant thereafter. In contrast, the albumin production by the monolayer markedly decreased after 4 days. The spheroid culture appears to be more suitable than the monolayer in studying differentiated functions of adult hepatocytes.

Albumins↗
PubMed1989

Development of heat-stable recombinant rinderpest vaccine.

Recombinant vaccinia virus (RVV) containing the full-length cDNA of rinderpest virus (RV)-haemagglutinin (H) gene was constructed. The H gene was inserted into the attenuated vaccine strain of vaccinia virus (VV), Le 16 m0, with two different promoters, namely cowpox virus A-type inclusion body (ATI) promoter or VV 7.5 kilodalton (P7.5) promoter. These RVVs produced the same sized fully glycosylated RV-H protein in RK 13 cells as that of the authentic RV-H. Their heat stability in the lyophylized state was similar to that of the parental VV. All rabbits immunized with these RVVs produced virus neutralizing (VN) antibody to RV as well as anti RV-H antibody. Four weeks after immunization, these animals were challenged with RV intravenously. None of the RVV-immunized rabbits developed any clinical signs of RV infection except one which was immunized with RVV containing the ATI promoter and developed low VN titer. These results indicate the possibility of developing a heat-stable recombinant vaccine for the eradication of rinderpest in tropical countries without cold storage systems.

Animals↗