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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 613 records · Page 34Linked to original sources
PubMed1987

Inhibitory mechanism of the proliferative response of B lymphocytes: suppression of the proliferation induced by anti-mu antibody and BSF1 by immune complexes.

We studied the effect of immune complexes (IC) on the responses of polyclonally activated murine B cells. For this, normal resting B cells were stimulated with the F(ab')2 fraction of goat anti-mouse mu-chain antibody and B-cell stimulating factor 1 (BSF1) after preculturing them with IC. Next, the relative membrane potential changes and the subsequent proliferative response were analysed. IC, particularly in antibody excess, inhibited both membrane depolarization and while those in antigen excess did poorly. Neither antigen nor antibody alone was effective. Inhibition was mediated via binding of IC to FcR gamma on B cells in a dose-dependent manner. Kinetic experiments showed that at least 6 hr was necessary for inducing the suppression of B-cell responses after binding of IC. We conclude that IC bound to FcR gamma on B cells regulates B-cell responses by acting on the initial step of activation.

Animals↗
PubMed1987

Retrospective histological studies on biopsied gastric lesions of patients in whom cancer was diagnosed at follow-up examination.

Serial biopsy specimens of gastric lesions of patients in whom cancer was diagnosed at follow-up examination were reexamined retrospectively; the source materials were 17,429 gastric biopsies carried out on 14,779 patients from 1971 to 1985 at Aichi Cancer Center Hospital. Among these cases, cancers were found at follow-up in 34 cases at locations distinct from the initially biopsied lesions, and in 41 cases, cancerous changes were detected at follow-up at the locations of the original lesions. These 41 cases amounted to 0.5% of the total biopsied cases with negative results. The average interval from the first to the last endoscopic examination in these 41 cases was 52.1 months and the longest interval was 150 months in the case of a scarred lesion. Based on the reexamination of the histology of the biopsy specimens taken at the first examination, these 41 cases were classified into three subgroups: 1) no precancerous atypical changes were observed, 2) doubtful precancerous changes were observed and 3) minute or slight malignant changes did exist but had been overlooked. The number of cases in the first category was 33 (80.5%), among which ulcer or its scar was most common, the number in the second category was 6 (14.6%), most of them being polypoid lesions, and the number in the third category was 2 (4.9%). Histological features of some cases in each subgroup are presented and the results are discussed.

Aged↗
PubMed1987

Absorption of theophylline from a sustained-release theophylline tablet formulation, Theo-Dur.

The absorption kinetics of theophylline after single oral administration of a sustained-release theophylline tablet formulation, Theo-Dur, were studied in healthy volunteers. The pharmacokinetic parameters were estimated by utilizing a one-compartment model with zero-order or first-order absorption according to the procedure "Praxis". The release of theophylline from the formulation in the in vitro dissolution study was shown to be an apparent zero-order process. The in vivo studies demonstrated that the time required to reach maximum plasma concentration of theophylline was about 8 h. The mean residence time in vivo, MRT, was 18.6 h. The present study also showed that the formulation was good sustained-release properties with adequate bioavailability and that the in vitro sustained-release characteristic was confirmed to be reflected in the plasma concentration-time profile of theophylline in the in vivo. The computer-predicted concentrations of theophylline based on the zero-order absorption model fitted to the observed data points better than those based on the first-order absorption model. The regression curves obtained by nonlinear least squares method based on the first-order absorption model underestimate the maximum observed plasma concentrations of theophylline. There was a highly significant relationship between observed and calculated around the maximum plasma concentration data based on the zero-order absorption model. These results show that the drug absorption from the formulation is best described by an apparent zero-order rather than a first-order absorption model.

Absorption↗
PubMed1987

[Flomoxef treatment of patients with respiratory tract infections].

Flomoxef (FMOX, 6315-S) was administered to 22 patients with respiratory tract infections. The patients consisted of 13 patients with pneumonia, 7 with bronchitis, 1 with bronchiectasis and 1 with pyothorax. The drug was administered by intravenous injection or intravenous drip infusion twice a day with doses of 1 to 2 g and total doses ranged from 17 to 64 g. The following results were obtained. 1. Clinical responses to the therapy were excellent in 1 case, good in 10 cases, fair in 4 cases, poor in 4 cases and not determined in 3 cases. Efficacy ratio was 57.9%. 2. As for adverse reactions, exanthema in 1 patient and stomatitis and numbness of tongue in another patient were observed, but these symptoms improved with cessation of the therapy. Abnormal laboratory test values were observed in 5 cases. From these results it appears that FMOX is a valuable antimicrobial agent against patients with respiratory tract infections.

Aged↗
PubMed1987

Cardiovascular pharmacology of 6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, a novel and potent cardiotonic agent with vasodilator properties.

The cardiovascular profile of 6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride (MCI-154), a novel cardiotonic agent structurally different from cardiac glycosides and beta-adrenoceptor agonists, was investigated in vivo. In anesthetized, open-chest dogs, MCI-154 (0.3-100 micrograms/kg i.v., bolus injection) produced dose-dependent increases in dP/dtmax and cardiac output, and decreases in arterial blood pressure and total peripheral resistance with a relatively small increase in heart rate. The positive inotropic effect of MCI-154 was more potent than those of amrinone and milrinone. In anesthetized, intact-chest dogs, infusion of MCI-154 (0.3-3 micrograms/kg/min i.v.) also exerted a positive inotropic effect. P.o. administrations of MCI-154 (10-300 micrograms/kg) increased dP/dtmax in conscious beagle dogs. The cardiotonic effect of MCI-154 was not attenuated by blockade of autonomic receptors, catecholamine depletion and prostaglandin synthesis inhibition. MCI-154 (0.3-30 micrograms i.a.) produced a direct vasodilator effect in the canine hind-limb. MCI-154 (3 and 30 micrograms/kg i.v.) was effective in heart failure models induced with high doses of propranolol or verapamil. The potent cardiotonic and vasodilator activities of MCI-154 revealed by the present study suggest that this agent would be an effective remedy for the treatment of heart failure.

Anesthesia↗
PubMed1987

[A clinical study on head injuries in the aged].

We review 79 patients over 65 years old among 715 patients who underwent CT scans in the early period after head injuries, to study the characteristics of head injury in the aged. Among 79 aged patients, 24 developed posttraumatic subdural fluid collections, and in 13 of them chronic subdural hematomas developed subsequently. There were only three acute epidural hematomas. However, a high incidence of intracerebral lesions was noted, regardless of the presence of skull fracture. The pedestrian accident was the most frequent cause of head injury in the 36 aged patients admitted and the mortality rate of traffic accident in the aged was also highest. The relationship between Glasgow Coma Scale Score (GCS) on admission and the outcome was not parallel in the aged, because high GCS not rarely resulted in poor condition or death. Head injury is apt to occur and becomes severe in the aged pedestrian because of advancing carelessness and dull movements with age. The vulnerability of the brain to the injury and changes of intracranial environment in the aged tend to cause intracranial lesions much more than in the younger patients. Already-existing diseases and/or posttraumatic general complications also make clinical courses worse in the aged. It seems important for the improvement of the treatment that the characteristics described above are always taken into consideration throughout the period of the treatment in the aged, in order to eliminate worsening factors adequately. In addition, the social measures to cope with the suffering of the aged pedestrians from traffic accident should be considered and established in an aging society.

Accidents, Traffic↗
PubMed1987

[A case of familial breast cancer--identical twin sisters with a heterochronic bilateral breast cancer that developed at the same age].

We have encountered very unique cases which involve identical twin sisters who underwent surgical treatment for a unilateral breast cancer at the same age of 28. Each, after 13 years, developed cancer in the opposite breast. In addition yet another sister, the youngest, had to undergo the same surgical procedure, at the same age that her identical twin sisters had had their first operations. These findings may indicate the existence of factors which decide the age of the malignancy onset, in addition to the existence of a predisposing factor for carcinoma in the genes of breast cancer patients.

Adult↗
PubMed1986

Production of a cytokine with interleukin 3-like properties and cytokine-dependent proliferation in human autologous mixed lymphocyte reaction.

The autologous mixed lymphocyte reaction (AMLR) was assayed in a medium containing fresh autologous serum, by using nylon-adherent stimulator cells and nonadherent responder T cells, which were prepared from human peripheral blood mononuclear cells in the absence of fetal calf serum (FCS) to avoid any sensitization to xenogeneic protein antigens. DNA replication without a background proliferative response was induced by stimulator cells in the responder cells. The addition of monoclonal anti-HLA-DR antibody to the culture or treatment of the responder cells with complement plus anti-T4 but not anti-T8 monoclonal antibody suppressed the AMLR, suggesting that this specific AMLR involves an interaction between HLA-DR antigens and helper/inducer T cells. Regardless of this specific DNA replication, the AMLR generated no production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), both of which could be found in the allogeneic (allo) MLR. In addition, DNA replication in the AMLR was not inhibited by the addition of specific antisera for IL-2 and IFN-gamma, both of which significantly inhibited the DNA replication in allo-MLR. The AMLR was accompanied by production of a soluble factor, which could stimulate the proliferation of murine interleukin 3 (IL-3)-dependent cell line 32Dcl but not the proliferation of IL-2-dependent cell lines. This factor was also found to be responsible for proliferation of responder nonadherent cells in the AMLR. It strongly stimulated bone marrow cells, as did the murine IL-3. The factor had an Mr range, as determined by gel filtration, of 15,000-28,000, but it did not bind to fast protein liquid chromatography (FPLC)-MonoQ column. Thus, the factor is distinguishable from IL-2 in physicochemical or biological properties, but similar to murine IL-3. These results suggest that the human AMLR may be primarily a phenomenon in which non-T cells mediated by the HLA-DR antigens on the cell stimulate helper/inducer T cells to produce a lymphokine with IL-3-like properties, but no IL-2, which in turn stimulates the factor-dependent cells to proliferate.

Antibodies, Monoclonal↗
PubMed1986

Induction of interleukin 3 but not interleukin 2 or interferon production in the syngeneic mixed lymphocyte reaction.

The syngeneic mixed lymphocyte reaction (SMLR) was assayed in the medium containing syngeneic normal mouse serum (NMS), by using nylon-adherent stimulator cells and nonadherent responder T cells, which were prepared from murine spleens in the absence of fetal calf serum (FCS) to avoid any sensitization to xenogeneic protein antigens. The responder cells in this SMLR, without definite background proliferation, generated specific proliferative response to the syngeneic stimulator cells in a dose-related fashion. The SMLR was accompanied by production of interleukin 3 (IL 3) but not interleukin 2 (IL 2) or interferon (IFN). No cytotoxicity against the syngeneic or allogeneic target cells was induced. Correlating with no production of IL 2 or IFN, no natural killer (NK) activity was detected. The proliferation was not inhibited by addition of specific antiserum for IFN-gamma. In contrast, proliferation in the responder cells when incubated with allogeneic stimulator cells was inhibited by anti-IFN-gamma serum and accompanied by production of IL 2 and IFN as well as IL 3, and by augmentation of NK activity and generation of cytotoxic T cells. Cell surface analysis revealed that the cells producing IL 3 in this SMLR system were Thy-1+ Lyt-1+2- helper T cells. Cells responding to the SMLR culture fluids with DNA replication were Thy-1-Lyt-1-2- asialo GM1- no-marker cells, which were the same as a population responsible for partially purified IL 3. On the other hand, when the responder cells were exposed to FCS before culture and assayed for SMLR in the FCS-free NMS medium, variable levels of IL 2 production were induced in response to the stimulator cells. The responder cells generated a high background DNA replication in the absence of syngeneic stimulators, suggesting that this IL 2 production may result from the stimulation of T cells by FCS as a foreign antigen. Overall, these results suggest that the SMLR may be a cellular interaction, in which non-T cells stimulate Lyt-1+2- helper T cells to produce IL 3 but not IL 2 or IFN. This IL 3 can, in turn, induce proliferation of IL 3 responding cells, which appear to be early precursors in lymphocyte differentiation, but no proliferative response or activation of IL 2- and IFN-dependent mature T cells or NK cells.

Animals↗
PubMed1986

Simulation analysis of excitation conduction in the heart: propagation of excitation in different tissues.

The normal excitation and conduction in the heart are maintained by the coordination between the dynamics of ionic conductance of each cell and the electrical coupling between cells. To examine functional roles of these two factors, we proposed a spatially-discrete model of conduction of excitation in which the individual cells were assumed isopotential. This approximation was reasoned by comparing the apparent space constant with the measured junctional resistance between myocardial cells. We used the four reconstruction models previously reported for five kinds of myocardial cells. Coupling coefficients between adjacent cells were determined quantitatively from the apparent space constants. We first investigated to what extent the pacemaker activity of the sinoatrial node depends on the number and the coupling coefficient of its cells, by using a one-dimensional model system composed of the sinoatrial node cells and the atrial cells. Extensive computer simulation revealed the following two conditions for the pacemaker activity of the sinoatrial node. The number of the sinoatrial node cells and their coupling coefficients must be large enough to provide the atrium with the sufficient electric current flow. The number of the sinoatrial node cells must be large so that the period of the compound system is close to the intrinsic period of the sinoatrial node cell. In this simulation the same sinoatrial node cells produced action potentials of different shapes depending on where they were located in the sinoatrial node. Therefore it seems premature to classify the myocardial cells only from their waveforms obtained by electrical recordings in the compound tissue. Second, we investigated the very slow conduction in the atrioventricular node compared to, for example, the ventricle. This was assumed to be due to the inherent property of the membrane dynamics of the atrioventricular node cell, or to the small value of the coupling coefficient (weak intercellular coupling), or to the electrical load imposed on the atrioventricular node by the Purkinje fibers, because the relatively small atrioventricular node must provide the Purkinje fibers with sufficient electric current flow. Relative contributions of these three factors to the slow conduction were evaluated using the model system composed of only the atrioventricular cells or that composed of the atrioventricular and Purkinje cells. We found that the weak coupling has the strongest effect. In the model system composed of the atrioventricular cells, the propagation failure was not observed even for very small values of the coupling coefficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Atrioventricular Node↗