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Biomedical subjects

T Masuda

Publications and source records attributed to T Masuda.

At least 361 records · Page 20Linked to original sources

Murine endothelial cell line cells, F-2: interaction with leukocytes and cytokines production.

Flowcytometry demonstrated that murine endothelial cell line F-2 expresses MHC class I antigen, FcR II, Mac-1 and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1) and class II antigen. However, co-culturing with TNF-alpha for 24 hr resulted in the increased expression of ICAM-1, and the decreased expression of VCAM-1. IL-1 alpha and IFN-gamma exerted this regulatory effect on VCAM-1 but not on ICAM-1. T (Con A blast) and B (LPS blast) cells adhered to F-2 cells at almost equal levels, and the adhesion was enhanced 20 to 50% when the cells were precultured with TNF-alpha for 24 hr. The inhibition assay using either (anti-ICAM-1 + anti-LFA-1, lymphocyte function-associated antigen-1) or (anti-VCAM-1 + anti-VLA-4, very late antigen-4) mAbs demonstrated that the ICAM-1 system was utilized more preferentially by T than B blasts when F-2 cells were stimulated with TNF-alpha, and the VCAM-1 system was vice versa under the unstimulated and stimulated conditions. Granulocytes also adhered to F-2 cells, but no mAbs could inhibit the adhesion. Although F-2 cells produced a considerable amount of IL-6, GM-CSF and neutrophil chemotactic activity, a 24 hr incubation with TNF-alpha resulted in an increase of 12 fold in IL-6 and 3 fold in neutrophil chemotactic activity production.

Animals↗

In vitro modification of human immunodeficiency virus type 1 (HIV-1) infectivity by the U937 cells.

The effect of host cell factors on infectivity of human immunodeficiency virus type 1 (HIV-1) was studied by infecting a monoblastoid cell line (U937) or a T-cell line (MOLT-4) with a highly infective single clone of HIV-1 and comparing the infectivity of the produced viruses to different cell lines. Chronically infected U937 cells consistently produced viruses with minimal infectivity. This phenotypic change was host-dependent as the back-passage of the U937-produced low infective viruses into MOLT-4 cells resulted in regaining their original high infectivity. Southern and Northern blot analyses of the HIV-1 grown in U937 cells did not reveal any genomic difference between it and the virus grown it MOLT-4 cells. The radioimmunoprecipitation analysis of viral proteins showed that the HIV-1-infected U937 cells had a different pattern of envelope glycoproteins and core proteins, which well correlated with the low infectivity of the produced viruses. This experimental system using MOLT-4 and U937 cell lines would be useful to further explore host cell factor(s) which play an important role in the regulation of HIV-1 infectivity.

Blotting, Northern↗

Interferon-gamma-producing tumor induces host tumor-specific T cell responses.

We investigated the mechanism of host immune responses against two interferon-gamma (IFN-gamma) gene-transduced tumors, plasmacytoma MOPC104E(Mu gamma) and mammary cancer SC115(K gamma), which originally had weak immunogenicity. Both IFN-gamma-producing tumor cells had reduced tumorigenicity and were rejected by syngeneic mice. The rejection was completely blocked by in vivo treatment with anti-CD8 or anti-IFN-gamma monoclonal antibodies. While anti-CD4 monoclonal antibody also blocked the rejection of SC115(K gamma), it enhanced the initial tumor growth of MOPC104E(Mu gamma). Specific protection against subsequent challenge with the respective parental tumor cells was demonstrated in mice which rejected the IFN-gamma-producing tumor cells. Cultured lymphocytes derived from immunized mouse spleens had cytotoxic T cell activity against parental tumor cells, as well as against cells that produced IFN-gamma. These findings indicate that the antitumor effects are mediated by cytotoxic T cells and, partly, by helper T cells, and that locally secreted IFN-gamma plays an important role in generating these effector cells.

Animals↗

Effect of recombinant human interleukin-11 on rat megakaryopoiesis and thrombopoiesis in vivo: comparative study with interleukin-6.

The ability of recombinant human interleukin-11 (IL-11) to stimulate rat megakaryopoiesis and thrombopoiesis in vivo was investigated. Once daily subcutaneous injections of IL-11 at doses of 2, 8 and 20 micrograms/rat for 5 d caused dose-dependent increases in platelet counts. The chronic administration of 20 micrograms/rat/d for 14 d resulted in biphasic increases in platelet counts with peaks at days 8 and 15 of up to 30% over the control, continuing for more than 5 d after cessation of IL-11 injections. Moreover, a striking increase in megakaryocytic size and ploidy in bone marrow in response to IL-11 was elicited. IL-11 induced a dose-dependent elevation in bone marrow cell numbers but not in splenic weight and cell numbers. Modifications of these parameters were noted as soon as 24 h after the first IL-11 injections. IL-11 had a same potency of thrombopoietic effect in rats as compared with IL-6. However, elevation of acute phase protein such as immunosuppressive acidic protein was 2.2-fold in rats given 20 micrograms/d of IL-6 over those receiving a same dose of IL-11 (470 v 210 micrograms/ml). In addition, the rate of body-weight increase in rats receiving IL-11 for 5 d as well as 14 d did not differ from that in control animals. In IL-6 treated rats, the increase in body weight was significantly slower than the controls, which was observed even in the group given 8 micrograms/d of IL-6. These results suggest that IL-11 may be an effective strategy for the treatment of thrombocytopenia.

Animals↗

Interspecies-specific ovarian autoantigens involved in neonatal thymectomy-induced murine autoimmune oophoritis.

PROBLEM: Thymectomy of mice on day 3 after birth (3d-Tx) gives rise to the appearance of a particular type of ovarian lesion known as experimental autoimmune oophoritis (AIO). METHOD: In the present study, the spleen cells from BALB/c mice having undergone 3 day-Tx AIO were fused with X63-Ag8-6.5.3 myeloma cells, and a number of hybridoma clones producing autoantibodies against ovarian tissue were established. RESULTS: On the basis of immunohistochemical and protein-chemical analysis, two independent clones, designated at T2.2 and S1.6, were found to react with interstitial tissues surrounding the follicles. These monoclonal antibodies showed broad cross-species reactivity, in that they recognized similar antigenic macromolecules in the rat, pig, human, and mouse. The antigenic determinants were strongly resistant to heat and acid, especially to the treatment of periodic acid, indicating that the antigenic determinants had no relation with carbohydrate components. CONCLUSIONS: By antibody affinity chromatography, two kinds of autoantigens were identified. SDS-PAGE, under reduced or nonreduced conditions, revealed an 80/85 kDa protein for T2.2, and an 82 kDa for S1.6, respectively.

Animals↗

Expression of monocyte chemoattractant protein 1 (MCP-1) in adult periodontal disease: increased monocyte chemotactic activity in crevicular fluids and induction of MCP-1 expression in gingival tissues.

The present study shows that monocyte chemotactic activity in crevicular fluids increases with severity of the disease and that a monocyte chemoattractant, monocyte chemoattractant protein 1 (MCP-1), is expressed as the predominant cytokine of gingival tissues and their fibroblasts treated with Porphyromonas (Bacteroides) gingivalis lipopolysaccharide (P-LPS). High monocyte chemotactic activity in the crevicular fluids was neutralized significantly by antiserum specific for the JE/MCP-1 protein. Marked expression of the MCP-1 gene was observed in the gingival tissues of all adult periodontal patients tested, but not in those of healthy subjects. Monocyte chemotactic activity was observed in culture supernatants of human normal gingival tissues treated with P-LPS, and the chemotactic activity increased in a dose-related manner. Expression of MCP-1 in P-LPS-treated human gingival fibroblasts was further examined. P-LPS induced the MCP-1 gene expression in a dose- and treatment time-dependent manner. The MCP-1 gene product in the culture supernatant was detected as two forms with molecular masses of 11,000 and 15,000 Da by immunoprecipitation with the specific antiserum. The MCP-1 gene expression was induced in the fibroblasts treated with interleukin-1 beta and tumor necrosis factor alpha, but not with interleukin-6. These results suggest that gingival fibroblasts can participate in monocyte recruitment in gingival tissues of adult periodontal patients via the MCP-1 gene product and that MCP-1 plays an important role in the inflammatory reaction in the disease.

Adult↗

Mouse mammary tumor virus with rearranged long terminal repeats causes murine lymphomas.

Mouse mammary tumor virus (MMTV) is a slowly transforming retrovirus associated primarily with the induction of mammary tumors. It is widely accepted that T-cell lymphomas of various mouse strains are associated with extra proviruses of MMTV. These extra proviruses showed site-specific rearrangements in the U3 region of long terminal repeats (LTRs), consisting of about 400 nucleotide deletions and occasional substitution resulting in unique tandem repeats. However, the question of whether these mutant MMTVs cause lymphomas has not been experimentally resolved. Here we present distinct evidence that they do. We constructed chimeric MMTVs by replacing the LTR of the recently constructed pathogenic MMTV provirus clone with rearranged LTRs of MMTV proviruses obtained from two DBA/2 mouse lymphoma cell lines, MLA and DL-8, and inoculated them into BALB/c mice. These mice developed lymphomas, but no mammary tumors, 4 to 11 months postinoculation, whereas the original pathogenic MMTV clone alone induced mammary tumors. These results showed that the tissue specificity of MMTV tumorigenesis is determined by the LTR structures.

Animals↗

Multiplicity of virus-encoded helper T-cell epitopes expressed on FBL-3 tumor cells.

To identify retroviral antigenic determinants recognized by CD4+ T helper cells during tumor rejection, we established four noncytolytic, helper-type, CD4+ T-cell clones by limiting dilution cultures of mixed lymphocyte-tumor cultures from mice immune to a Friend virus-induced tumor, FBL-3. Among these, three T helper cell clones were isolated from C57BL/6 mice and the fourth was isolated from a (BALB/c x C57BL/6)F1 mouse. All these clones proliferated in response to the immunizing FBL-3 tumor cells in a major histocompatibility complex class II-restricted manner. Each clone expressed a distinct T-cell receptor with a characteristic combination of alpha and beta chains. The localization of helper T-cell determinants on viral proteins was analyzed with recombinant vaccinia viruses expressing Friend murine leukemia virus (F-MuLV) gag or env genes or shorter fragments of the env gene. Epitopes recognized by these T-cell clones were mapped to at least two distinct portions in the env region of the F-MuLV genome. These epitopes were identified more precisely with synthetic peptides derived from the F-MuLV envelope protein sequence. One of these epitopes was common to Friend and Moloney MuLVs and was located in the N-terminal region of the gp70 glycoprotein at amino acids 122 to 141. The second epitope, which was recognized in the context of hybrid I-Eb/d major histocompatibility complex class II molecule, was located close to the C-terminal end of gp70 at amino acids 462 to 479. In addition, a possible third epitope was located in the N-terminal half of the gp70 sequence and differed from the first epitope in that it was not cross-reactive with the Moloney MuLV envelope protein.

Amino Acid Sequence↗

Dexamethasone modulation of ion transport and fluid movement across airway epithelium.

Electrolyte or fluid is secreted across airway mucosa by both superficial epithelium and submucosal glands. To understand the effect of glucocorticoid on fluid movement across airway mucosa, we examined the effects of dexamethasone (Dex) on bioelectric properties of canine and feline tracheal epithelium and on 22Na efflux from isolated feline tracheal submucosal glands. Potential difference (PD) and short-circuit current (SCC) across tracheal epithelium were measured using an Ussing chamber, and conductance (G) was calculated as the ratio SCC/PD. Isolated glands were loaded with 22Na, and the rate constant (RC) of Na2+ efflux was calculated by measuring the radioactivity of each effluent sample. After treatment with 10(-9) to 10(-5) M Dex for up to 6 h, the epithelium and isolated glands were stimulated with isoproterenol (ISP) and methacholine (MCh), respectively. Dex treatment did not alter significantly baseline values of PD, SCC, or RC. However, Dex treatment produced a dose-dependent attenuation of ISP-evoked epithelial PD and SCC and of MCh-evoked glandular RC. In canine epithelium, pretreatment with 10(-5) M Dex for 6 h reduced by 40% the ISP (10(-6) M)-evoked rise in PD and SCC, whereas G remained unchanged. After 10(-5) M Dex treatment for 6 h, MCh (10(-5) M)-evoked RC in isolated glands was significantly less than in control glands (MCh alone) by 23%. These findings suggest that glucocorticoid decreases the fluid secretion across the airway mucosa, especially when the mucosa are stimulated.

Animals↗

Colocalization of corticotropin-releasing factor and vasopressin in the paraventricular nucleus of the human hypothalamus.

The anatomical relationship between corticotropin-releasing factor (CRF)-containing cells and arginine vasopressin (AVP)-containing cells in the human hypothalamus was investigated by immunocytochemistry. In the paraventricular nucleus of the hypothalamus (PVH), CRF-like immunoreactivity (CRF-LI) was present exclusively in parvocellular cells, while AVP-like immunoreactivity (AVP-LI) was present in both parvocellular and magnocellular cells. No CRF-immunoreactive neurons were observed in the supraoptic nucleus. All CRF-immunoreactive parvocellular cells in the PVH were also AVP immunoreactive. We confirmed the presence of AVP in the CRF-immunoreactive cells by using two kinds of anti-AVP antisera, one of which recognized the side chain of AVP while the other recognized the ring structure of AVP. Colocalization of CRF-LI and AVP-LI was observed not only in the same perikarya but also in the same nerve fibers of parvocellular cells. The present results raise the possibility that AVP and CRF may be secreted together into the human portal circulation.

Adolescent↗

New interpretation of systolic time intervals from active cross-bridge model.

Using an active cross-bridge model proposed by the authors, it has been established theoretically that cross-bridge activation rate (Ka) of the left ventricular myocardium, which might correspond to the rate of binding of Ca2+ with troponin C, is approximately expressed as a simple formula: Ka = 3/electromechanical systole (sec-1), although no definitive biological proof has yet been provided for the equation. One hundred eighteen patients without significant cardiac disease and 6 patients who had atrioventricular block with a permanent pacemaker were evaluated to determine the Ka value of the normal human left ventricular myocardium (test 1), and to examine the effect of changes in heart rate (test 2) as well as afterloading (test 3) or dobutamine infusion (test 4) on Ka. The pacing rate was increased from 50 to 110 beats/min at 20-beat increments in test 2. Arterial pressure was elevated by angiotensin II infusion in test 3, and 7 subjects received a continuous dobutamine infusion in test 4. The Ka value was found to be related to heart rate, to be increased by dobutamine infusion, and to be decreased by myocardial lengthening due to afterloading. Dependence of Ka on heart rate appeared to result from changes in myocardial length. The Ka value corrected for heart rate (Kac) had an average variation of only 4.6%, and was unrelated to age or myocardial length in individual subjects. Thus, the Kac value of normal human left ventricular myocardium appears to be nearly constant between individuals but to be increased by catecholamine infusion or myocardial shortening.

Adult↗

Plasma lipoprotein(a) levels and fibrinolytic activity in patients with unstable angina.

The relationship between plasma Lipoprotein(a) (Lp(a)) levels and plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (t-PA) antigen levels were studied in 15 patients with unstable angina. Plasma levels of Lp(a) (mg/dl) were significantly higher in patients with unstable angina after treatment 2 weeks than on admission (19.7 +/- 2.8 vs 14.6 +/- 2.3, p < 0.01). On the other hand, the plasma levels of PAI activity (IU/ml) and t-PA antigen (ng/ml) in patients with unstable angina were significantly higher on admission than after treatment (PAI activity: 11.4 +/- 1.4 vs 7.7 +/- 1.5, t-PA antigen: 8.7 +/- 0.9 vs 7.0 +/- 0.9, p < 0.01). We conclude that patients with unstable antigen have reduced fibrinolytic capacity, as indicated by increased PAI activity, and that the plasma Lp(a) level may be decreased due to binding with fibrin during the acute stage of unstable angina.

Adrenergic beta-Antagonists↗

Quantitative assessment of a change of hemosiderin deposition with age in splenic compartments of rats.

Hemosiderin deposition was quantitatively estimated in paraffin sections stained using Perls' iron reaction in the spleens of untreated male rats aged from 0 to 28 months. Hemosiderin was deposited in the periarteriolar lymphocyte sheath (PALS), lymph follicles, and marginal zone, as well as in the red pulp which was the main compartment of hemosiderin deposition. Special attention was paid to the PALS and marginal zone. Marked hemosiderin deposition was evident from 4 months, although only few hemosiderin-laden macrophages appeared in the first 3 months. Hemosiderin deposition peaked at 12 months in the red pulp and at 20 months in the white pulp and marginal zone. The deposition in the white pulp and marginal zone was about 1/9 to 1/4 of that in the red pulp. A few hemosiderin-laden macrophages were found in the lymph follicles after 2 months. In the periarterial region of the splenic hilus, deposition of hemosiderin granules was observed even at 1 month when there was little hemosiderin deposition elsewhere. Since no arteries open there, the presence of hemosiderin-laden macrophages in the PALS and lymph follicles suggested movement of some macrophages from the red pulp and/or the marginal zone. In addition, hemosiderin deposition in the PALS increased with age after it decreased in the other compartments.

Aging↗

Relationship of anthropometric indices of body fat to cardiovascular risk in Japanese women.

The relationship between body fat indices and cardiovascular risk was analyzed in 97 Japanese women aged 36-72 years. The variables used were anthropometric measures of body fatness, blood lipids and blood pressure. Total adipose tissue weight (TATW) was estimated from bioelectrical impedance measurements. Subcutaneous adipose tissue weight (SATW) was calculated by measuring subcutaneous fat thickness at 14 sites using a skinfold caliper. The indices of body fat distribution were the ratios of waist to hip circumference (WHR) and abdominal to hip circumference (AHR). Blood pressure and serum lipid levels were determined in all subjects after an overnight fast. The correlations among the various body fat indices were high, and all were strongly correlated with WHR and AHR; only % SATW and percentage internal adipose tissue weight (%IATW) were not correlated with WHR and AHR. Significant positive associations were found between WHR, triglycerides and systolic blood pressure (SBP). Negative associations were found between WHR and HDL-cholesterol (HDL-ch.) and the ratio of HDL-ch. to total cholesterol (HDL-ch./T-ch.). On the other hand, significant positive associations were found between AHR, T-ch., LDL-cholesterol, free fatty acid and SBP. A negative association was found between AHR and HDL-ch./T-ch.. Partial correlations were used to determine further associations between cardiovascular risk factors and fat distribution indices. SBP was associated with WHR or AHR after removing the effects of age. Similarly, HDL-ch./T-ch. was associated with WHR or AHR after removing the effects of age and degree of obesity (BMI). These results suggest that the WHR and AHR are equally valid estimates of body fat distribution with respect to their relationship with cardiovascular risk. These relationships occurred independently of age or BMI in Japanese women. These findings emphasize the importance of intra-abdominal obesity as a metabolic risk factor for cardiovascular disease associated with a high WHR and AHR.

Adipose Tissue↗

[The effect of aerobic exercise training on internal body fat in obese women].

A group of 11 obese women (from 13% of ideal weight and higher) volunteered to participate in a study designed to reduce weight in a 92-day program of aerobic exercise. Before and after the weight reduction period, body fat indices were measured by deuterium oxide (D2O) dilution and by skinfold anthropometry. Changes in internal body fat and subcutaneous fat were calculated. Mean weight loss was 3.6 +/- 1.2 kg, and internal body fat and subcutaneous fat were 1.8 +/- 1.3 kg (21.2%) and 3.0 +/- 0.9 kg (16.0%), respectively. Highly significant correlation were obtained between changes in internal body fat and total body fat (r = 0.856, p < 0.001). However, changes in internal body fat were not significantly associated with changes in waist to hip ratio (WHR). In the present study, we found that changes in total body fat were significantly related to changes in internal body fat during treatment of obesity with aerobic exercise. However, changes in internal body fat were not valid estimates of changes in body fat distribution in relation to changes in WHR.

Adipose Tissue↗

[Muscle fiber conduction velocity in right and left biceps brachii for badminton players].

The purpose of this study was to investigate the laterality of muscle fiber conduction velocity in biceps brachii for badminton players, who have stronger arm in the handedness side for long term training. The muscle fiber conduction velocity was calculated from the propagation time of the action potentials along the muscle fibers and the electrode separation using cross-correlation method. For badminton players, significant lateral differences (e.g. right side skillful) were observed in the upper arm girth (P < 0.01) and isokinetic peak torque at 0, 10, 20, 30, 40 rpm (P < 0.01). For control subjects, significant lateral differences were in upper arm girth (P < 0.05) and isokinetic peak torque at exactly 30 rpm (P < 0.05). As for muscle fiber conduction velocity, there were no statistically significant differences between right (4.16 +/- 0.34 m/sec) and left (4.08 +/- 0.34 m/sec) sides in badminton players, and the control group exhibited same tendency (right: 4.36 +/- 0.25 m/sec, left: 4.28 +/- 0.33 m/sec) as well. These results suggest no training-induced change in the muscle fiber conduction velocity.

Adult↗

Prevention of autoimmune diabetes with lymphotoxin in NOD mice.

We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats. In this study, we examined the effect of LT, which is structurally and functionally related to TNF, on NOD mice with diabetes. The cumulative incidence of diabetes at 30 wk of age was 22 of 40 (55%) in nontreated female NOD mice and was 4 of 8 (50%; NS), 3 of 29 (10%; P < 0.001), and 0 of 8 (0%; P < 0.001) in female mice treated three times a week from 4 to 30 wk of age with 5, 50, or 500 U of recombinant hLT, respectively. Intensity of insulitis was slightly reduced in the long-term LT-treated mice. LT productivity by ConA-stimulated spleen cells was examined in vitro. Although no significant difference was found between NOD mice and the other mouse strains, female NOD mice were slightly but significantly (P < 0.01) lower producers of LT immunoreactivity than male NOD mice, the diabetes incidence of which is lower than that of females. The SMLR as a marker of normal immune response, which was reported to be impaired in autoimmune animals including NOD mice, was significantly lower in female than male NOD mice. However, the low SMLR in female NOD mice was significantly increased by the administration of LT, and the increase was mediated by the responder cells of the LT-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analysis of vocal abuse: fluctuations in phonation time and intensity in 4 groups of speakers.

We have seen many patients with a voice disorder due to vocal abuse. However, there is little information about the speaking behaviour of such patients. The object of this study was to analyze speaking behaviour and to evaluate the relationship between the cause of voice disorders and its effects on speech. We had previously measured phonation time with a speech time accumulator. Recently, we have developed a speech intensity/speech time accumulator. We obtained data by accumulating the phonation time at 4 degrees of vocal intensity, ranging from weak to strong. By using this instrument, we measured the speaking habits of 29 subjects for 131 days and collected data about the criteria for vocal abuse. Our results showed that the office workers exhibited a phonation time (33.6 +/- 13.6 min for 8 h) three times shorter than that of teachers and patients with vocal fold nodules (102.1 +/- 22.9 min for 8 h). For the teachers and patients with a long phonation time, half of the total phonation time was at high intensity.

Acoustics↗