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Biomedical subjects

S Tsuru

Publications and source records attributed to S Tsuru.

At least 37 records · Page 2Linked to original sources

[Current and future perspectives of medical information network systems for community health using personal computers and IC cards].

Recent developments in computer and communication technology were studied in relation to medical information network systems, using computers and IC cards, to solve problems in community health. Trial use of personal computer network systems among physicians and IC card systems for personal health data management are already in existence in some parts of Japan. These trials were studied and analyzed based on a questionnaire survey of physicians and patients. Results of the study produced some useful points that should be considered when introducing these systems. These included: 1) details on expectations and specifications for these systems by physicians and patients, 2) easy access to valuable information is a key point for active network systems among physicians, 3) plausibility of improvement of communication between physicians and patients by using these systems, 4) recognition that an important problem concerns patient information privacy and must be considered before introducing these systems. A study of practical merits of these systems and methodology for realization indicates that participation by active and attractive providers of information can be expected to stimulate frequent use of the network system. The cost of introducing these systems can be partially borne by eliminating the large investment now allocated for processing requests for reimbursement of medical services. Investigation into the introduction of medical information systems provides a good opportunity to elucidate problems in the present medical systems.

Computer Communication Networks↗

Increased mitochondrial uptake of rhodamine 123 by CDDP treatment.

Rhodamine 123 (R 123) is a positively charged dye at physiological pH that accumulates specifically in the mitochondria of living cells without cytotoxic effect. In the present study, the uptake of R 123 by EL-4 lymphoma cells in culture with anticancer agents was measured by flow cytometry. Changes in R 123 uptake during the cultivation period were compared with cell distribution at different phases of the cell cycle. According to the increase in the proportion of S phase cells, mitochondrial synthesis increased, giving rise to a maximal fluorescence intensity of about 1.3-fold. Synchronous cultures showed the same relationship between increased mitochondrial uptake of R 123 and the S phase fraction as was observed in normal cultures. After treatment with 10(-3) M 5-fluorouracil (5-FU) for 1 h, EL-4 cells showed an increased binding of R 123 per cell followed by an accumulation of early S phase cells transiently. However, uptake of R 123 decreased 24 h later. On the contrary, after treatment with 10 micrograms/ml of cis-diamminedichloroplatinum (CDDP), a G2 + M block was observed from 12 h of reseeding and accumulation of the G2 + M cells continued. In this case, high uptake of R 123 continued during the observation period. From these results, mitochondrial synthesis seemed to increase according to the increment in proportion of S phase when the acceleration of the cell cycle turnover was augmented or the cycle was blocked in S phase by 5-FU. CDDP inhibited the cell division at G2 + M phase and caused increased R 123 fluorescence per cell. The stainability of R 123 may indicate the activity of cell division and may be a good way of evaluating the efficacy of antitumor drugs on the cells.

Cell Cycle↗

Enhancement of host defense by Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, a novel synthetic compound. A comparison with recombinant human granulocyte colony-stimulating factor in 5-fluorouracil-treated mice.

The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell.

Adjuvants, Immunologic↗

AIDS-like disproportion of minor T-cell subsets in Japanese patients with Wegener's granulomatosis.

Fifteen Japanese patients with Wegener's granulomatosis (WG) were evaluated according to their lymphocyte subset abnormalities. Two colour immunofluorescent flow cytometry was used to distinguish the lymphocyte subset alterations. WG group showed a decrease in the percentage of CD4+ cells and the increase of CD8+ cells. Within the NK cell family, the functionally unidentified CD8+57+ cells were markedly elevated. The disproportion of the lymphocyte subsets (CD4+ decreases CD8+57+ increases) were similar to those of Acquired Immunodeficiency Syndrome (AIDS) and AIDS relating complexes (ARC). To assess silent infection of Human immunodeficiency virus (HIV), the polymerase chain reaction (PCR) was done for all patients to selectively amplify specific HIV proviral DNA sequences in peripheral blood mononuclear cells, HIV-1 proviral DNA was not found in any patients but these changes of WG might suggest a possible adaptive response to unknown viral infection.

AIDS-Related Complex↗

Is injectable collagen truly safe?

Most patients have no response to injectable collagen or silicone, but some cases may have positive or 'undersea' (= clinically negative but immunologically positive) response to collagen. From the results of the Macrophage migration inhibition test, the relative immunogenicity was augmented most when we used implants with the following combination. The first immunization was collagen and the second one was collagen with silicone. The augmented antigenicity might be enough to cause an allergic reaction to the patients who had no response to each implant alone.

Adjuvants, Immunologic↗

Intracellular hydrogen peroxide production by peripheral phagocytes from diabetic patients. Dissociation between polymorphonuclear leucocytes and monocytes.

Although the standard assays for reactive oxygen species have been based on the measurement of those released into the extracellular environment, the microbicidal capacity to the engulfed microorganisms is mainly dependent on those released into the intracellular environment, such as phagosomes. We studied intracellular oxidative activities of individual phagocytes by dichlorofluorescein (DCFH) oxidation assay to investigate the relationship between the reactive oxygen species released intracellularly and the impaired microbicidal capacity in diabetic patients. Time courses of intracellular production of hydrogen peroxide by polymorphonuclear leucocytes (PMNL) and monocytes were observed at the resting condition and after the stimulation with phorbol myristate acetate (PMA; 160 nM) by flow cytometry. Thirty-four patients with non-insulin-dependent diabetes mellitus (NIDDM) and 23 age-matched healthy volunteers were subjected to the studies. PMNL from patients with NIDDM showed a significantly decreased capacity to produce hydrogen peroxide after the stimulation (P less than 0.05 at 15 min, P less than 0.01 at 30 and 45 min). By contrast, intracellular hydrogen peroxide production by monocytes at the resting condition and an early stimulatory phase (8 min after the stimulation) was significantly (P less than 0.01) enhanced in patients with NIDDM compared with that in controls. Both the changes of intracellular hydrogen peroxide production observed in PMNL and monocytes from patients with NIDDM were in association with an increased haemoglobin Alc level in erythrocytes, but did not relate to total cholesterol and triglyceride levels in the serum. The possible mechanisms of these dissociated changes in hydrogen peroxide producing capacity of phagocytes from patients with NIDDM are discussed.

Adult↗

Reduced CD4-CD8 T cell ratios in patients with Wegener's granulomatosis.

All of the patients with Wegener's granulomatosis (WG), whom we studied, exhibited abnormalities in lymphocyte subsets. We used two-color immunofluorescence flow cytometry to examine the lymphocyte subset alterations. WG group showed a decrease in the percentage of CD4+ cells and an increase of CD8+ cells. Within the NK cell family, functionally unidentified CD8+57+ cells were markedly increased in number. The disproportion of these lymphocyte subsets (CD4+ decreases, CD8+57+ increases) was similar to that seen in Acquired Immunodeficiency Syndrome (AIDS) and AIDS related complex (ARC).

Adult↗

[Structure of communication between physicians and patients from the viewpoint of community health].

Understanding the structure and problems of communication between physicians and patients should be achieved before introducing a medical information network system for community health. To this end a questionnaire survey was performed on 2,362 patients who saw physicians in medical facilities in a certain district of Hiroshima city. As a result, it was revealed that 'explanations given by doctors' and 'explanatory ability of patients' were mutually closely related and formed a basis for other aspects of communication and patient behavior. Satisfaction with the explanation given by physicians declined with examination time of less than 5 minutes and examination in hospitals rather than in clinics. Explanatory ability of patients decreased as age of patients increased and showed a remarkable decrease in patients of more than 80 years old. This suggested the existence of risk that information necessary for safe examinations may not be transmitted to physicians. These results pointed out the importance of a supporting system of communication especially for the elderly patient.

Communication↗

Depression of early protection against influenza virus infection by cyclophosphamide and its restoration by protein-bound polysaccharide.

Relationship between depression of early protection against influenza virus infection and the decrease in the number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice was investigated using protein-bound polysaccharide (PSK), which had been shown to exert a potent restorative effect on leukocytopenia in immunocompromised hosts. Following intranasal inoculation with influenza virus (1.5 x 10(3) PFU) into untreated mice, the pulmonary virus titer progressively increased during 3 days and decreased gradually from the day 7 after infection. The treatment of mice with cyclophosphamide (150 mg/kg) 2 days before infection markedly enhanced the pulmonary virus multiplication from the early phase of infection, and the higher virus titer was maintained thereafter. When mice were given cyclophosphamide after PSK-treatment, virus titers from the early to late phases of infection were lower than those in untreated mice.

Adjuvants, Immunologic↗

[Production of reactive oxygen species by rat alveolar macrophages. Dissociation between the intracellular and extracellular release of hydrogen peroxide].

In order to clarify the features of reactive oxygen species produced by rat alveolar macrophages (AMs), the concentrations of intracellular and extracellular hydrogen peroxide were measured under various experimental conditions. Intracellular hydrogen peroxide was measured by DCFH method using a flow cytometer, while the extracellularly released fraction was measured by scopoletin method using a spectrophotometer. The concentration of intracellular hydrogen peroxide after stimulation with opsonized zymosan (10 micrograms/ml) was significantly higher than that after stimulation with phorbol myristate acetate (PMA; 100 ng/ml). On the other hand, hydrogen peroxide released extracellularly after stimulation with PMA was significantly greater that that after stimulation with opsonized zymosan. These results indicate that the soluble membrane stimulant and the phagocytic particles have different mechanisms in activating the production of hydrogen peroxide in AMs. That is, hydrogen peroxide induced by PMA was mainly released extracellularly, while that induced by zymosan was mainly released into the intracellular environment. At rest, the concentration of intracellular hydrogen peroxide in rat AMs was high. Potassium cyanate, a known mitochondrial inhibitor, suppressed the intracellular hydrogen peroxide in AMs not only at rest but also after stimulations, indicating that most of the reactive oxygen species released into the intracellular environment in AM are produced by mitochondria. From these results, in order to gain a closer insight into the function of AMs, it is very important to distinguish the oxidative metabolites produced intracellularly which are related to bactericidal function from those of the extracellularly released fraction which give rise to lung damage.

Animals↗

Effects of macrophage colony-stimulating factor on reduction of viable bacteria and survival of mice during Listeria monocytogenes infection: characteristics of monocyte subpopulations.

Mice could well tolerate infection with a lethal dose of Listeria monocytogenes after intraperitoneal preinjections with 250 micrograms of macrophage colony-stimulating factor (M-CSF) per kg of body weight for 5 days. The characteristic changes in the surface markers (Mac-1, LFA-1, and F4/80) of peripheral monocytes were also investigated in order to analyze the mechanism of protection by M-CSF. This investigation shows the excellent effect of intraperitoneal preinjections of M-CSF on the reduction of viable Listeria organisms and the improvement of survival after an intravenous Listeria infection.

Animals↗

Enhanced resistance against Listeria monocytogenes achieved by pretreatment with granulocyte colony-stimulating factor.

Phagocytosis, H2O2 production, Mac-1 expression, and in vivo elimination of Listeria monocytogenes were enhanced in granulocyte colony-stimulating factor (G-CSF)-treated mice. Transfer of polymorphonuclear leukocytes prolonged survival of mice infected with a lethal dose of L. monocytogenes. G-CSF augments the functions of polymorphonuclear leukocytes and thus plays a role in protection.

Animals↗

Flowcytometric measurement of the cell cycle of experimental tumors: some devices for accurate measurement of proliferative activity.

In this paper we present the cell cycle analysis using the latest flowcytometer, FACScan and dedicated softwares. Although the 5-bromodeoxyuridine (BrdU) and anti-BrdU method developed by Gratzner has become popular for analysis of cell kinetics, contaminating interstitial cells and cell doublets are still factors responsible for some mistakes in measuring the cell cycle accurately. These hampering cells were almost gated out on the catogram consisting of the forward scatter and DNA content (propidium iodide, PI). After that, the bivariate distribution of BrdU and PI according to the tumor growth showed reliable patterns. In LLC tumor the population, of which DNA content was compatible with S phase cells, was detected in the cytogram. Thus, the two-dimensional analysis of the cell cycle can demonstrate each population clearly. The results obtained from the BrdU method are more beneficial than autoradiography or microspectrophotometry, and reproducible data of the cell cycle parameters can be acquired with some devices described here.

Adenocarcinoma↗

Protective effect of elastase on cis-platinum-induced renal toxicity.

The protective effects of elastase (Ela) and fosfomycin against renal toxicity of cis-diamminedichloroplatinum (II) (CDDP) were evaluated in an experimental study using rats. When Ela was used concomitantly with CDDP, the elevation of urinary N-acetyl-beta-D-glucosaminidase levels in the early phase and the sharp fall in these levels in the latter phase were prevented. It was also found that the blood urea nitrogen levels and serum creatinine levels were significantly lowered. Histologically, atrophic and necrotic changes in the tubular epithelium were prevented. The total serum platinum levels showed no change with the addition of Ela; however, the platinum levels in the renal tissues were significantly reduced. These results suggested that Ela is effective against platinum deposits in the renal tissues, particularly in the tubular epithelium, thus protecting the kidneys. On the other hand, fosfomycin demonstrated no such positive results suggestive of a protective effect on the renal function parameters or during histological observation.

Acetylglucosaminidase↗

Effects of combined therapies with protein-bound polysaccharide (PSK, Krestin) and fluorinated pyrimidine derivatives on experimental liver metastases and on the immunologic capacities of the hosts.

An experimental model is introduced for the study of liver metastases using intrasplenically injected EL-4 and Lewis lung tumor cells. Fluorinated pyrimidine derivatives, 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil, showed inhibitory effects on the frequencies of liver metastases. Immunosuppressive effects of these drugs were compared at the doses capable of showing 50% inhibition of the development of metastatic nodules. These derivatives strongly suppressed the phagocytic activity and the number of Kupffer cells of the liver and then the humoral response against sheep red blood cells, the delayed hypersensitivity against picryl chloride. On the contrary, combined administration of protein-bound polysaccharide (PSK) and 1-(2-tetrahydrofuryl)-5-fluorouracil showed no inhibitory effect on these activities.

Adjuvants, Immunologic↗

[Augmentation of activities of peripheral granulocytes and of resistance against bacterial infection after administration of G-CSF into mice].

We evaluated the metabolic capability of murine peripheral granulocytes after administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by quantitative flow cytometric assay for H2O2-dependent oxidative product formation. Intraperitoneal administration of a daily dose of 10 micrograms of rhG-CSF for 5 days induced doubling of the leukocyte population. Differential counting of peripheral leukocytes and scattergram by flow cytometry showed an increased mature granulocyte population. After stimulation with phorbol myristate acetate, the granulocytes of the rhG-CSF-administered mice demonstrated some hyperresponsive population and an increased H2O2 production. The hyperresponsive population showed H2O2 production 4-6 times higher than did normal cells. Granulocytes from the G-CSF-treated mice revealed an augmented phagocytic activity and an increased expression of Mac-1 molecules. Moreover, mice treated with G-CSF showed an enhanced resistance against intravenous infection with a lethal dose of E. coli. Granulocytes showing such markedly increased oxidative metabolism may be a significant component of the host defence to various infective organisms.

Animals↗

Thymic depletion in pregnancy: kinetics of thymocytes and immunologic capacities of the hosts.

In the present study we observed a significant depression of thymocytes during pregnancy and investigated the influences of this thymic change on the immunologic capacities of peripheral lymphocytes. Thymocytes in pregnant mice began to decrease in number from Day 10 and reached about 0.1-fold of the nonpregnant level at Day 19, just before parturition. At late stage of pregnancy, thymocyte subpopulation expressing CD4+CD8+ and Thy1.2+PNA+ was selectively depressed. On the contrary, peripheral lymphocytes including splenocytes, peripheral blood lymphocytes and peripheral lymph node cells showed no depression. As to the immunologic capacities of the pregnant hosts, delayed footpad reaction and phagocytic activity of fixed liver macrophages in vivo were remarkably suppressed, but MLR reactivity and antibody response to SRBC or haptens were well preserved. Transfer of pregnant sera or administration with steroid hormones especially E3 into nonpregnant mice induced similar changes in the thymus and peripheral lymphocytes in number and subsets but this could not mimic the immunologic reactivities of the pregnant mice. These results suggest that sex steroid hormones such as E3 play an important role in the changes in cell populations of each lymphoid organ and the immune reactivities of the hosts during pregnancy. However, other factors also contribute to the immunologic capacities of the maternal hosts.

Animals↗