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Biomedical subjects

R Sasaki

Publications and source records attributed to R Sasaki.

At least 199 records · Page 11Linked to original sources

Relationship between serum xanthophyll levels and the consumption of cigarettes, alcohol or foods in healthy inhabitants of Japan.

The relationship between serum concentrations of beta-cryptoxanthin and zeaxanthin and the consumption of cigarettes and alcohol or the intake frequencies of foods was investigated in 775 Japanese inhabitants. Serum concentrations of beta-cryptoxanthin and beta-carotene in healthy Japanese aged 40-70 years were higher in females than in males. Serum beta-cryptoxanthin levels were inversely associated with the consumption of cigarettes and alcohol, as were the serum beta-carotene levels. Serum zeaxanthin (including lutein) levels were associated with cigarette consumption. The levels of serum beta-cryptoxanthin were positively correlated with the intake frequency of some fruits, and those of zeaxanthin, with the intake frequency of green vegetables, milk and eggs. These xanthophylls may play a role with beta-carotene in smoking-related cancer prevention.

Adult↗

Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium.

The effect of human recombinant erythropoietin (Epo) on B cell responses was studied in a serum-free medium. Epo enhanced IgM production and thymidine uptake by a human IgM-producing lymphoblastoid cell line, CBL. This effect was specific to Epo since enhancement was blocked by anti-Epo antibody but not by control antibody. Among the various cytokines, interleukin-4 (IL-4) enhanced IgM production and thymidine uptake while IL-6 enhanced IgM production without affecting thymidine uptake. In contrast, other cytokines including IL-1 beta, IL-2, IL-5, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), or granulocyte/macrophage colony-stimulating factor (GM-CSF) were without effect. However, the enhancing effect of Epo is different from that of IL-4 or IL-6, since Epo effect was not blocked by anti-IL-4 antibody or anti-IL-6 antibody. Moreover, specific binding of Epo was detected on CBL cells. Epo also enhanced immunoglobulin (IgG, IgM and IgA) production and thymidine uptake by purified tonsil small resting B cells stimulated by Staphylococcus aureus Cowan strain I (SAC) or by large activated B cells. In contrast, Epo had no effect on unstimulated small resting B cells. These results indicate that Epo could directly stimulate activated and differentiated B cells and could enhance B cell immunoglobulin production and proliferation.

Antibodies, Monoclonal↗

Effects of the consumption of cigarettes, alcohol and foods on serum concentrations of carotenoids, retinol and tocopherols in healthy inhabitants living in a rural area of Hokkaido.

The relationship between serum concentrations of carotenoids, tocopherols and retinol and the consumption of cigarettes, alcohol and foods was investigated in 835 healthy inhabitants (aged 35-79 years) of a rural area of Hokkaido. Serum concentrations of beta-carotene (BC), alpha-carotene (AC), lycopene (LY), beta-cryptoxanthin (BX), zeaxanthin (including lutein, ZX), canthaxanthin (CX) and beta-tocopherol (including gamma-tocopherol, BT) were higher in females than in males, while serum retinol (RE) concentrations were lower. Serum alpha-tocopherol (AT) concentrations were the same for both sexes. The serum values of BC, BX, AC, LY and ZX for males were inversely associated with the consumption of cigarettes in multiple-regression analysis. The serum values of BC, AC and BX for males were inversely associated with alcohol consumption, while serum RE values were positively related to alcohol consumption for both sexes. There were significant relations between serum values of BC, AC, and ZX and the intake frequencies of carrots, tomatoes, milk and/or green-leaf vegetables, especially for females, and between serum BX values and the intake of oranges, juices and fruits. Serum RE and AT concentrations were not associated with any food intake, and BT concentrations were associated with the intake of tomatoes and juices for males.

Adult↗

[A method of interval estimation for number of patients in the nationwide epidemiological survey on intractable diseases].

A method for estimating the intervals for the number of patients with intractable diseases from nationwide epidemiological surveys was developed under the assumption that response is independent of frequency of patients. This method is based on data utilizing the number of response hospitals classified by their reported number of patients. The approximate 95% confidence intervals of numbers of several intractable diseases patients were estimated using this method.

Data Interpretation, Statistical↗

Factor with erythroid burst-promoting activity in human urine unlike other hematopoietic growth factors.

A factor with burst-promoting activity (BPA) stimulates the formation of erythroid bursts in the presence of erythropoietin, acting on early erythroid progenitor cells (erythroid burst-forming units, or BFU-E). Here we investigated the biological properties of this factor partially purified from the urine of anemic patients. The human urinary factor did not cause the formation of late erythroid progenitor cells (erythroid colony-forming units, or CFU-E) or enhance such colony formation in the presence of erythropoietin. Thus, the urinary factor was a different substance from erythroid potentiating activity and from activin, which act on both BFU-E and CFU-E. The urinary factor promoted the colony formation of BFU-E from both humans and mice, but the human hematopoietic growth factors such as recombinant interleukin-3, interleukin-6, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor did not stimulate the formation of BFU-E derived colonies from mice. The results suggested that the factor in the urine of anemic patients was different from the hematopoietic growth factors identified so far.

Anemia↗

Quantitative assay of terminal deoxynucleotidyl transferase (TdT) activity using monoclonal antibodies.

Terminal deoxynucleotidyl transferase (TdT) is an important marker for the diagnosis and the therapy of leukemia and lymphoma patients. In this study, we developed the quantitative method for the assay of TdT antigen in leukemic cells using a combination of monoclonal and polyclonal antibodies prepared for this enzyme. High correlation was obtained between the values measured by biochemical assay and enzyme-linked immunosorbent assay (ELISA). This method (ELISA), using antibodies to TdT, permits the rapid and quantitative estimation of TdT antigen in leukemic cells.

Antibodies, Monoclonal↗

[The incidence of pulmonary tuberculosis in an urban area].

The incidence and prevalence of pulmonary tuberculosis has declined steadily in Japan, but the trends differ greatly by area according to epidemiological status. We studied the incidence and trends of pulmonary tuberculosis in an urban area (population approx. 150,000) during the period of 1979-1988. The area studied is a part of a large commercial city, characterized as having the most prevalent rate of tuberculosis area in that city. Of 1245 newly registered cases, 80% were over 40 years of age. While the incidence rate decreased to 57% in the last 10 years in this area, compared to 69% decrease for all of Japan, it was still considerably higher than the national average. Especially in the 20-59 age group it continued to be 2 times higher than that of the whole of Japan. Moreover, the positive rate of tubercle bacilli at the time of registration had increased remarkably from 27% in 1979 to 62% in 1988. These results suggest the tuberculosis continues to be a significant problem in this urban area, although the steady decline in the incidence of tuberculosis had led to a lack of awareness of this disease.

Adolescent↗

Serum concentrations of carotenoids, retinol, and alpha-tocopherol in healthy persons determined by high-performance liquid chromatography.

Serum concentrations of alpha-carotene (AC), beta-carotene (BC), lycopene (LY), beta-cryptoxanthin (CR), zeaxanthin (including lutein. ZX), canthaxanthin (CX), retinol (RE), and alpha-tocopherol (TO) in healthy persons (618 males and 1,196 females) aged 7-86 years were determined by HPLC. Serum concentrations of BC among persons aged 20-49 years were higher with increasing age in females, but not in males. Serum CR concentrations decreased with age ranging from 7 to 39 years, while ZX concentrations rose in the age group of 20 to 59 years for both sexes. In contrast, serum RE concentrations and ratios of RE/BC and RE/CR, especially in males aged 20-49, were higher with age. Serum TO values in both sexes rose with age and were similar.

Adolescent↗

Establishment of an erythroid cell line (JK-1) that spontaneously differentiates to red cells.

The authors established a new hemopoietic cell line (JK-1) from a patient with chronic myelogenous leukemia in erythroid crisis. This JK-1 line predominantly consists of immature cells, but a small number of mature erythroblasts and red cells can be consistently seen without any specific differentiation inducer. The JK-1 cells grow in suspension culture supplemented with human plasma and carry double Philadelphia chromosomes. Hemoglobin staining with benzidine was positive for about 20% of cells and the type of the hemoglobin was for the most part HbF. Surface-marker analysis revealed JK-1 cells positive for glycophorin A, EP-1, and HAE9. The proportion of mature cells was elevated by the addition of delta-aminolevulinic acid. Erythropoietin (EPO) enhanced the growth of JK-1 cells either in the suspension or in methylcellulose semisolid culture. The total number of EPO receptors was 940 per cell, of which 220 sites had an affinity higher than the other 720 sites. This is the first report of an established human erythroid cell line which spontaneously undergoes terminal differentiation.

Antigens, Surface↗

Expression of the erythropoietin receptor on a human myeloma cell line.

We demonstrated the expression of the erythropoietin (EPO) receptor by a human myeloma cell line (MM-S1) which was established in our laboratory. EPO dose-dependently stimulated the proliferation of MM-S1 cells. Binding of radioiodinated EPO (125I-Epo) to MM-S1 cells was competitively inhibited by unlabeled EPO, but not by other recombinant cytokines. Specific binding of 125I-Epo to MM-S1 cells was saturable, and the Scatchard analysis revealed 330 EPO binding sites per cell with a Kd of 0.56 nmol/L. Bound EPO was internalized by MM-S1 cells during incubation at 37 degrees C. This is the first report describing the expression of the EPO receptor by human cells other than those of the erythroid lineage.

Cell Division↗

Activity and gene expression of transglutaminase in guinea pig liver during the postnatal growing phase.

During the postnatal growing phase from birth to 7 weeks old, the cytosolic transglutaminase activity of guinea pig liver increased 3.8-fold. The enzyme activity in the particulate fraction increased slightly. Immunoblot analyses showed that the postnatal increase in the activity was correlated with in increase in the enzyme protein. The quantity of mRNA of the liver transglutaminase did not change significantly during the postnatal growing phase examined. These results indicated that transglutaminase may be involved in the postnatal development of guinea pig liver and that the amount of transglutaminase in the postnatal liver may be controlled post-transcriptionally.

Animals↗

The role of carbohydrate in recombinant human erythropoietin.

1. Recombinant human erythropoietin has N-linked sugar [Tsuda et al., (1988) Biochemistry 27, 5646-5654]. Here we have demonstrated the presence of O-linked sugar (0.85 mol/mol erythropoietin) composed of sialic acid and Gal beta(1-3)GalNAc. 2. To investigate the role of these sugars, erythropoietins deglycosylated to different extents were prepared using specific glycosidases. Sugars are not essential for in vitro biological activity of erythropoietin, because the fully deglycosylated erythropoietin had the full activity when assayed with in vitro bioassay methods. Asialylation yielded erythropoietin with higher affinity to the receptor than the undigested hormone and therefore an increased in vitro activity. Although erythropoietin from which N-linked or total sugars were removed also had higher affinity for the receptor, their in vitro activity remained unchanged compared with that of the undigested erythropoietin for unknown reasons. On the other hand, removal of sialic acids or N-linked sugar abolished the in vivo biological activity completely, indicating that the presence of N-linked sugar with terminal sialic acids is required for the hormone to reach target sites; full deglycosylation resulted in total loss of the in vivo biological activity of erythropoietin. 3. Incubation of asialo-erythropoietin and fully deglycosylated recombinant human erythropoietin at 70 degrees C for 15 min decreased the biological activity to 35% and 11% of the initial activity, respectively, while the undigested erythropoietin lost no activity. Thus resistance of erythropoietin to thermal inactivation is largely due to the presence of sugars, and terminal sialic acids greatly contribute to the stability.

Animals↗

Expression of guinea-pig liver transglutaminase cDNA in Escherichia coli. Amino-terminal N alpha-acetyl group is not essential for catalytic function of transglutaminase.

Transglutaminases (EC 2.3.2.13) catalyze the formation of epsilon-(gamma-glutamyl)lysine cross-links and the substitution of a variety of primary amines for the gamma-carboxamide groups of protein-bound glutamine residues. These enzymes are involved in many biological phenomena. Transglutaminase reactions also have been shown to be suitable for applied enzymology. In this study, as a first step of studies to elucidate the structure/function relationship of transglutaminase, we constructed an expression plasmid, pKTG1, containing a cDNA of guinea-pig liver transglutaminase between the NcoI and PstI sites of an expression vector, pKK233-2, and produced the liver transglutaminase as an unfused protein in Escherichia coli. The purified recombinant enzyme was indistinguishable from natural liver transglutaminase in some structural properties such as molecular mass, amino acid composition, and amino- and carboxyl-terminal sequences. However, the alpha-amino group of the amino-terminal alanine residue of the recombinant transglutaminase was not acetylated as was that of the natural enzyme. Comparison of the recombinant enzyme with the natural one did not indicate significant differences in specific activity and apparent Km values for substrates in the histamine incorporation into acetyl alpha s1-casein. The sensitivity to activation by Ca2+ and the rate of catalyzed protein cross-linking were also similar between recombinant and natural transglutaminases. These results indicated that the N alpha-acetyl group in natural liver transglutaminase has not a particular role in the catalytic function of this enzyme.

Acetylation↗

Computed tomographic findings of nasopharyngeal carcinoma with skull base and intracranial involvement.

Twenty-nine patients with nasopharyngeal carcinoma (NPC) with skull base or intracranial involvement were analyzed by high-resolution computed tomography (CT). We divided the path of the primary tumor spread into six directions from the nasopharynx. The most common direction of spread was the anterior region, and the second most common was the posterolateral region. Recently, high resolution CT has been used for the diagnosis of the nasopharynx. T-staging of NPC was made according to the International Union Against Cancer (UICC) TNM classification system, depending on clinical findings and conventional radiograph examinations (not including CT). CT images were valuable for detection of the primary tumor involvement of the skull base region in NPC. Furthermore, bone target CT images were better for searching for subtle bony changes. Therefore, we recommend that CT should be used in T-staging of NPC systematically. When CT is used as one of the staging criteria, some patients with NPC with subtle bony changes will be upstaged.

Adolescent↗

S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon.

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs. 108.9 +/- 8.2 nmol/gm liver in controls (p less than 0.005). The depletion was corrected with S-adenosyl-L-methionine (0.4 mg/kcal) administration (102.1 +/- 15.4 nmol/gm after S-adenosyl-L-methionine-ethanol, with 121.4 +/- 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 +/- 0.13 mumol/gm after ethanol vs. 4.87 +/- 0.36 mumol/gm in controls) that was attenuated by S-adenosyl-L-methionine (3.89 +/- 0.51 mumol/gm in S-adenosyl-L-methionine-methanol vs. 5.22 +/- 0.53 mumol/gm in S-adenosyl-L-methionine controls). There was a significant correlation between hepatic S-adenosyl-L-methionine and glutathione level (r = 0.497; p less than 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 +/- 21.4 IU/L vs. 13.4 +/- 1.8 IU/L; p less than 0.001, whereas in a corresponding group of animals given S-adenosyl-L-methionine with ethanol, the values were only 30.3 +/- 7.1 IU/L (vs. 9.6 +/- 0.7 IU/L in the S-adenosyl-L-methionine controls). This attenuation by S-adenosyl-L-methionine of the ethanol-induced increase in plasma glutamic dehydrogenase (p less than 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Polyadenylic acid polymerase activity in chronic myelogenous leukemia.

Poly(A) polymerase activity was markedly elevated in CML in the blastic phase, moderately high in the accelerated phase and low in the chronic phase. The activity was significantly higher in the myeloid crisis than in the lymphoid crisis and elevated with increasing ratio of blasts in leukemia cases. In TPA or retinoic acid-treated leukemia cells poly(A) polymerase activity was decreased. These results suggest that poly(A) polymerase activity changes, depending on the maturation of leukemic cells and the assay of this enzyme activity may be useful for the early detection of the exacerbation of CML cases.

Blast Crisis↗

Changes in serum concentrations of beta-carotene and changes in the dietary intake frequency of green-yellow vegetables among healthy male inhabitants of Japan.

Serum levels of beta-carotene among 147 healthy male inhabitants were measured twice with an interval of one year in order to determine the relationship between changes in serum beta-carotene levels and changes in the dietary intake of green-yellow vegetables. A positive association was found to exist between changes in the intake frequency of green-yellow vegetables and changes in serum beta-carotene levels, whereas changes in alcohol intake and smoking were discovered to be negatively associated with changes in serum beta-carotene levels. The positive association between changes in the intake frequency of green-yellow vegetables and changes in serum beta-carotene levels was preserved after adjustment for these negative factors.

Adult↗