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Biomedical subjects

S Kitagawa

Publications and source records attributed to S Kitagawa.

At least 199 records · Page 11Linked to original sources
PubMed1992

[Phase II clinical study on 99mTc-GSA, a new agent for functional imaging of the liver].

Phase II study of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes, was performed in 81 patients with liver diseases to validate its safety and possibility for the evaluation of hepatic function. None of adverse reactions, abnormal clinical laboratory findings and anti-99mTc-GSA antibody production due to 99mTc-GSA was recognized. Immediately after the injection of 99mTc-GSA, the dynamic data and serial hepatic images were obtained for 60 min. The indices for blood clearance and liver accumulation were calculated based on the counts in the regions of interest on the hearts and livers. In 54 patients with chronic hepatic disorders such as liver cirrhosis, the blood clearance and liver accumulation of 99mTc-GSA were retarded according to the progress of the hepatic disorders. The findings of 99mTc-GSA scintigraphy also reflected the hepatic functions of the patients with large hepatic tumors, obstructive jaundice and acute hepatitis. These results suggest that 99mTc-GSA has the clinical potentials to evaluate the liver functions in the patients with hepatic disorders.

Adult↗
PubMed1992

Interventional embolization with fibrin glue for a large inferior mesenteric-caval shunt.

We report an unusual case of a large inferior mesenteric-caval shunt in a 25-year-old man without cirrhosis with hypoproteinemia and hypochromic anemia. In this large shunt the direct communication was between the inferior mesenteric vein and the internal iliac vein. Hemodynamic change as a result of the shunt was thought to cause his present clinical problems and future portosystemic encephalopathy. Percutaneous transcatheter embolization of the shunt with fibrin glue was performed through the internal iliac vein, and this offered amelioration of hypoproteinemia and reduction of serum ammonia levels without any complications. An interventional radiologic approach instead of surgical ligation should be attempted for portosystemic shunts, and fibrin glue, as well as coils or a detachable balloon, is also valuable as an embolizing material.

Adhesives↗
PubMed1991

[Clinical application of asialoglycoprotein receptor-mediated liver scintigraphy using 99mTc-DTPA-galactosyl-human serum albumin].

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptors on the hepatocytes. Studies were performed in three normal volunteers and 19 patients with chronic liver diseases. Serial scintigrams and time-activity curves of heart and lever were obtained for 60 min following a single intravenous injection of 99mTc-GSA (1 mg/185 MBq). % Injected dose (%ID) in the blood at 60 min after injection and that in the liver were determined. Excellent hepatic images were obtained for 60 min in normal subjects, and neither blood pool image nor extrahepatic uptake was recognized. In the studies of patients, however, blood pools were also visualized in various degrees suggesting altered receptor quantity, although the livers were visualized clearly. The %ID in the blood at 60 min after the injection showed significant correlations with serum albumin levels (r = -0.741, p less than 0.0001), retention rates of ICG at 15 min (r = 0.855, p less than 0.0001), plasma disappearance rates of ICG (r = -0.760, p less than 0.0005), prothrombin times (r = -0.696, p less than 0.002), hepaplastin tests (r = -0.575, p less than 0.05), total bilirubin levels (r = 0.689, p less than 0.001) and Child Turcotte scores (r = 0.769, p less than 0.0001). Significant differences of %ID in both blood and liver were observed between normal subjects and patients in accordance with severities of the hepatic disorders. These results suggest that 99mTc-GSA liver scintigraphy is useful in evaluating the liver function.

Adult↗
PubMed1991

Stimulation and priming of human neutrophils by interleukin-8: cooperation with tumor necrosis factor and colony-stimulating factors.

Interleukin-8 (IL-8) stimulated an increase in cytoplasmic-free Ca2+ ([Ca2+]i) and intracellular pH (pHi) in parallel at low concentrations (0.5 to 5 ng/mL), and stimulated O2- release and membrane depolarization in parallel at high concentrations (50 to 5,000 ng/mL). IL-8-induced O2- release was potentiated by tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF) in a dose-dependent manner, whereas it was inhibited by cyclic AMP agonists. These characteristics and the time-courses of the responses stimulated by IL-8 were similar to those stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP), except that the cells stimulated by IL-8 showed shorter duration and less magnitude in some responses. In addition, IL-8 was found to be a potent priming agent and to enhance O2- release stimulated by FMLP. The priming effect of IL-8 was very rapid and was maximal within 5 minutes of preincubation. The dose-response curves for priming were identical to those for triggering of an increase in [Ca2+]i and pHi. The potency of the maximal priming effects on FMLP-induced O2- release was TNF greater than GM-CSF greater than IL-8 greater than G-CSF. The combination of IL-8 and the suboptimal concentrations of TNF or GM-CSF resulted in the additive priming effect, whereas the combination of the optimal concentration of IL-8 and the optimal concentration of TNF, GM-CSF, or G-CSF resulted in the effect of more potent priming agent alone. These findings suggest that IL-8 stimulates or primes human neutrophils according to its concentrations and cross-talks with TNF, GM-CSF, G-CSF, or FMLP at the inflammatory sites.

Adult↗
PubMed1991

Heterogenous graft rejection pathways in class I major histocompatibility complex-disparate combinations and their differential susceptibility to immunomodulation induced by intravenous presensitization with relevant alloantigens.

The present study investigates the heterogeneity of graft rejection pathways in class I major histocompatibility complex (MHC)-disparate combinations and the susceptibility of each pathway to immunomodulation induced by intravenous presensitization with alloantigens. Depletion of CD8+ T cells was induced by repeated administration of anti-CD8 monoclonal antibody. CD8+ T cell-depleted mice failed to generate anti-allo class I MHC cytotoxic T cell (CTL) responses but exhibited anti-allo class I MHC T cell responses, such as mixed lymphocyte reaction (MLR)/IL-2 production, that were induced by CD4+ T cells. In contrast, donor-specific intravenous presensitization (DSP), as a model of donor-specific transfusion, induced almost complete elimination of CD4+ and CD8+ T cell-mediated MLR/IL-2 production, whereas this regimen did not affect the generation of CTL responses induced by DSP-resistant elements (CD8+ CTL precursors and CD4+ CTL helpers). Prolongation of skin graft survival was not induced by either of the above two regimens alone, but by the combination of these. Prolonged graft survival was obtained irrespective of whether the administration of anti-CD8 antibody capable of eliminating CTL was started before or after DSP. The combination of DSP with injection of anti-CD4 antibody also effectively prolonged graft survival. However, this was the case only when the injection of antibody was started before DSP, because such antibody administration was capable of inhibiting the generation of CTL responses by eliminating DSP-resistant CD4+ CTL helpers. These results indicate that (a) the graft rejection in class I-disparate combinations is induced by CD8+ CTL-involved and -independent pathways that are resistant and susceptible to DSP, respectively; (b) DSP contributes to, but is not sufficient for, the prolongation of graft survival; and (c) the suppression of graft rejection requires an additional treatment for reducing DSP-resistant CTL responses. The results are discussed in the context of potential clinical application in attempts to inhibit the generation of DSP-resistant CTL responses upon the prospective DSP.

Animals↗
PubMed1991

Heterogeneity of CD4+ T cells involved in anti-allo-class I H-2 immune responses. Functional discrimination between the major proliferating cells and helper cells assisting cytotoxic T cell responses.

MLR in various combinations with class I H-2 disparity revealed that there are three patterns of MLR in the aspect of responding T subset (CD4 vs CD8) dominance. Irrespective of the CD8 vs CD4 dominance, a single i.v. administration of class I-disparate allogeneic spleen cells resulted in almost complete abrogation of anti-class I proliferative capacity of both CD4+ and CD8+ T cells in six combinations. The suppression of proliferative responses was correlated with the striking reduction in the ability to produce IL-2 upon stimulation with the relevant class I alloantigens. In contrast, i.v. presensitized recipient mice exhibiting only marginal MLR/Il-2 production could generate comparable magnitudes of anti-allo class I CTL as well as graft rejection responses to those induced by normal unpresensitized mice. The administration in vivo of anti-CD4 antibody along with the i.v. presensitization not only suppressed the generation of CTL responses by spleen cells but also induced appreciable prolongation of allo-class I-disparate skin grafts under conditions in which neither alone did it. These results demonstrate that 1) the suppression of graft rejection responses is not necessarily reflected on the reduction of MLR; 2) CD8+ CTL precursors responsible for graft rejection can be activated by either allo-class I-reactive CD8+ or CD4+ Th cells; 3) i.v. presensitization induces functional elimination of CD8+ and CD4+ proliferative/IL-2-producing T cells but not of CD8+ CTL precursors and CD4+ Th whose capacity is expressed by assistance of CTL induction but not by their own proliferation. Thus, this study illustrates the heterogeneity of class I alloantigen-reactive CD4+ T cells in the aspect of their capacity to proliferate themselves vs contribute to CTL induction as well as graft rejection.

Animals↗
PubMed1991

Asymmetry of membrane fluidity in the lipid bilayer of blood platelets: fluorescence study with diphenylhexatriene and analogs.

Membrane fluidity of bovine platelets was examined with diphenylhexatriene (DPH), its cationic trimethylammonium derivative (TMA-DPH) and anionic propionic acid derivative (DPH-PA). After addition of these probes to platelet suspensions at 37 degrees C, the fluorescence intensity of DPH-PA reached equilibrium within 2 min, whereas those of DPH and TMA-DPH increased gradually. With increase in the fluorescence intensity of TMA-DPH, its fluorescence anisotropy decreased significantly, but the fluorescence anisotropies of DPH-PA and DPH did not change during incubation. The gradual increase of fluorescence intensity of TMA-DPH was due to its penetration into the cytoplasmic side of the platelet membrane, as shown quantitatively by monitoring decrease in its extractability with albumin. Transbilayer movement of TMA-DPH was markedly temperature-dependent, and was scarcely observed at 15 degrees C. The fluorescence intensity of TMA-DPH was much higher in platelet membranes and vesicles of extracted membrane lipids than the initial intensity in intact platelets. Moreover, the fluorescence anisotropy of TMA-DPH was much lower in the former preparations than the initial value in intact platelets. These results suggest that binding sites for TMA-DPH in the cytoplasmic side of the platelet membrane are more fluid than those in the outer leaflet of the plasma membrane. Platelet activation by ionomycin induced specific change in the fluorescence properties of TMA-DPH without causing transbilayer incorporation of the probe.

Animals↗
PubMed1991

The lymphoid cell populations required for induction of tolerance of different subsets of alloantigen-reactive T cells.

Previous studies have demonstrated that i.v. presensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bml (bml) spleen cells induced potent suppression of anti-bml CD8+ T cell-mediated responses in vitro as well as suppression of the allograft response. The present study analyzes the population of donor bml cells required for suppression of the generation of the cellular subsets involved in the in vitro and in vivo immune responses. Anti-bml CD8+ helper T cell (proliferative/IL-2-producing) activities were almost completely eliminated by i.v. inoculation of bml whole blood or various (T or B cell) fractions of spleen cells. However, anti-bml CD8+ cytotoxic T lymphocyte capacity was significantly reduced by i.v. sensitization with bml T cell-containing, but not with T cell-depleted splenic fractions. In B6 mice receiving bml skin grafts following i.v. sensitization with T-depleted bml spleen cells, marginal Th activity was induced. However, the CTL response was equal to that observed in unsensitized mice, and allograft survival was not prolonged. Prolongation of bml graft survival was achieved by i.v. presensitization with bml T cell fraction, indicating that bml T cells were a requirement for suppression of graft rejection in the B6-bml combination. In contrast, in the B6-C-H-2bml2 (bml2) combination in which CD4+ T cells are responding to bml2 alloantigens, only the B cell fraction was capable of prolonging bm12 graft survival. These results indicate that functionally and phenotypically different subsets of alloantigen-reactive T cells are rendered unresponsive by i.v. presensitization with distinct fractions of donor lymphoid cells.

Animals↗
PubMed1991

Polymorphonuclear leukocyte-induced detachment of cultured epidermal carcinoma cells from the substratum.

In an in vitro study, intended to develop tumoricidal therapy with the use of human leukocyte, an interesting phenomenon was found. Normal human polymorphonuclear leukocytes (PMN) plated on a cell line established from malignant trichilemmal cyst (DJM-1), a kind of squamous cell carcinoma, in a serum-free media and incubated for 48 h induced the detachment of DJM-1. The detachment was more extensive as the number of PMN increased. The detachment rate was 97.0% when the number of PMN and DJM-1 in a well was in a ratio 2.4:1 and the viability of detached DJM-1 was 96.5%. Two kinds of proteinase inhibitors, especially the inhibitor of neutrophil elastase, fetal bovine serum, and monoclonal anti-laminin antibody inhibited the detachment significantly. Furthermore, when PMN were seeded in a chamber with a filter membrane bottom to prevent direct contact with DJM-1, DJM-1 detachment decreased to 14.2%. In view of these results, the following mechanism was postulated. Activated by their adhesion to DJM-1, especially between laminin receptor on PMN and laminin on DJM-1, PMN secreted proteinases, resulting in DJM-1 detachment. This phenomenon might be an expression of cytotoxicity of PMN to cancer cells, because cultured cancer cells of epithelium origin such as DJM-1 can grow only after they are firmly attached to the substratum. This phenomenon, in turn, may explain the final step in the induction of epidermal-dermal separation in subepidermal bullous diseases with PMN infiltration such as bullous pemphigoid and dermatitis herpetiformis if we could regard DJM-1 as normal keratinocyte.

Carcinoma, Squamous Cell↗
PubMed1991

Enhanced neutrophil functions in a patient with colony-stimulating activity-producing lung cancer.

We studied neutrophil functions in a patient with colony-stimulating activity (CSA)-producing lung cancer. A 59-year-old man had an abnormal chest X-ray and leucocytosis, predominantly with neutrophils. Pneumonectomy was performed, and the histological diagnosis of the tumour was large-cell carcinoma of the lung. The tumour induced marked granulocytosis in tumour-transplanted nude mice, and the conditioned media of the tumour contained very strong human-active CSA. Superoxide release and membrane depolarization in neutrophils stimulated by the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine, were markedly enhanced in the patient. These findings suggest that CSA produced by the tumour primed neutrophil functions in vivo in the patient.

Animals↗
PubMed1991

Inhibitory effects of catechol derivatives on arachidonic acid-induced aggregation of rabbit platelets.

Pyrocatechol and other non-substituted dihydric phenols, which have strong redox power, inhibited arachidonic acid-induced aggregation of rabbit platelets at much lower concentrations than those at which these phenols inhibited stable prostaglandin endoperoxide, U46619-induced aggregation. Among non-substituted dihydric phenols, pyrocatechol was most potent. In order to clarify the physicochemical properties of the phenolic compounds which control the inhibitory potencies of dihydric phenols, we observed the inhibitory effects of 3- and 4-substituents of pyrocatechol on arachidonic acid-induced platelet aggregation. Among seven derivatives tested, the inhibitory effect of 4-C6H5-substituent was strongest and 4-COOH-substituent was weakest. Inhibitory effects of the catechol derivatives were well correlated with the quotients of their hydrophobicities and oxidation-reduction potentials. Inhibitory effects of hydroquinone and resorcinol were also on the same correlation line. These results suggest that the inhibitory effects of catechol derivatives and other dihydric phenols are controlled by two physicochemical properties: oxidation-reduction potential and hydrophobicity.

Animals↗
PubMed1991

Aclacinomycin, an anti-leukemic anthracycline, impairs human neutrophil functions.

The effects of aclacinomycin, an anti-leukemic anthracycline, on human neutrophil functions were investigated. The release of superoxide (O2-) in neutrophils stimulated by opsonized zymosan, myristate, or phorbol myristate acetate was inhibited by aclacinomycin in a dose- and time-dependent manner. The phagocytosis of yeast particles and oil droplets, and membrane potential changes stimulated by phorbol myristate acetate were also inhibited by aclacinomycin. On the other hand, the O2(-)-producing enzyme (NADPH oxidase) in the particulate fraction prepared from myristate-stimulated neutrophils was not affected by aclacinomycin. When high concentrations of aclacinomycin (10-100 micrograms/ml) were employed, significant inhibition of O2- release, phagocytosis, and membrane potential changes was observed within 5 min. Phagocytic activity was also inhibited when neutrophils were preincubated for 13 h at 37 degrees C with a low concentration (40 ng/ml) of aclacinomycin, which could be obtained by intravenous administration of 20 mg aclacinomycin. Myristate-induced O2- release was not impaired by cytosine arabinoside (2-800 micrograms/ml), vincristine (0.1-100 micrograms/ml), adriamycin (25-100 micrograms/ml), or daunomycin (5-75 micrograms/ml) when the cells were preincubated with these drugs for 5 min at 37 degrees C. These findings suggest that aclacinomycin inhibits the respiratory burst by impairing the activating system of NADPH oxidase and phagocytic activity.

Aclarubicin↗
PubMed1991

[Effect of posture on pharyngeal area measured by acoustic reflection technique].

Patients with obstructive sleep apnea (OSA) have a smaller pharyngeal area (PA) and higher compliance than normal subjects. The apnea-hypopnea index (AHI) in OSA patients determined by polysomnographic study was greater in the supine than lateral position. Recently there have been reports of reduction in the PA by the acoustic reflection technique (ART) in the supine position. However, there has been no report on the PA measured by ART in the lateral position which is important in the treatment of OSA. To evaluate differences in the PA with posture changes, we measured the PA in 41 normal subjects (11 males and 30 females) in the sitting, lateral and supine positions by ART. The average PA in the sitting position in the males and females was 3.8 +/- 0.6 cm2, and 3.3 +/- 0.5 cm2, respectively. The average PA in the lateral position in the males and females was 3.5 +/- 0.6 cm2, and 3.1 +/- 0.5 cm2, respectively. The average PA in the supine position in the males and females was 2.9 +/- 0.5 cm2, and 2.7 +/- 0.4 cm2, respectively. PA in the sitting position correlated well with body surface area (BSA). The average PA in both the males and females was significantly smaller in the supine than in the sitting position. The average PA in the lateral position in both males and females was significantly smaller than that in the sitting position and was significantly larger than that in the supine position. Decrease in PA with posture (from sitting to lateral) in the males (9.2 +/- 5.5%) was similar to that in the female (5.7 +/- 5.4%). Decrease in PA with posture (from sitting to supine) was significantly larger in male (24.4 +/- 9.5%) than in female (16.6 +/- 6.8%). We conclude that the decrease of PA in the supine position is ameliorated in the lateral position in normal subjects. Lateral position may be the preferred sleeping position in snoring or OSA patients.

Adult↗