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Biomedical subjects

J Seki

Publications and source records attributed to J Seki.

At least 19 recordsLinked to original sources
PubMed1992

Pentamidine: a non-peptide GPIIb/IIIa antagonist--in vitro studies on platelets from humans and other species.

In this paper we show that the non-peptide anti-parasite agent pentamidine is a broad spectrum anti-platelet agent with an IC50 of 1.1 microM in ADP-induced platelet aggregation in human platelet rich plasma (PRP). It had similar activity when collagen, arachidonic acid, platelet activating factor, thrombin and epinephrine were used. It had no effect on platelet intracellular cAMP levels. It inhibited 125I-fibrinogen, 125I-fibronectin and 125I-von Willebrand factor binding to ADP-activated fixed platelets with IC50 values of 160, 160 and 60 nM respectively. Pentamidine showed a high degree of species selectivity with slightly less activity in monkey and dog PRP and little activity in guinea pig, rabbit, rat and mouse PRP compared with human. This was similar to the other RGD analogues tested. This species specificity was shown to be dependent on the species of platelets and independent of the species of fibrinogen. Thus, pentamidine is a potent non-peptide inhibitor of fibrinogen binding to GPIIb/IIIa.

Amino Acid Sequence↗
PubMed1992

TFC-612, a prostaglandin E1 derivative, enhances fibrinolytic activity in rats.

TFC-612 inhibited thrombus formation on wire coils inserted into the lumen of the inferior vena cava of rats after 5 oral doses of 1.0 and 3.2 mg/kg and subcutaneous doses of 1.0 and 3.2 micrograms/rat/hr. This compound showed slight inhibition of platelet aggregation induced by collagen at 1.0 and 3.2 mg/kg (po) and significant inhibition at 10 mg/kg. TFC-612 had no effect on the plasma coagulation system at 3.2 mg/kg. Conversely, oral doses of 0.32-3.2 mg/kg dose- dependently enhanced fibrinolytic activity as measured by euglobulin clot lysis time and lysis area on fibrin plates by euglobulin fraction. TFC-612 did not enhance fibrinolytic activity in vitro. These results suggest that the enhancement of fibrinolytic activity by TFC-612, which may be due to an increase in tissue plasminogen activator release or reduction of plasminogen activator inhibitors release, contributes to its inhibition of thrombus formation.

Alprostadil↗
PubMed1992

Inducibility of protein-reactive antibodies by peptide immunization: comparison of three epitope peptides of hen egg-white lysozyme.

Three epitope peptides of hen egg-white lysozyme (HEL) were tested for ability to induce antibodies reactive with native HEL. Each peptide was coupled to bovine gamma-globulin (B gamma G) and 4 rabbits were immunized with each peptide-B gamma G conjugate in complete Freund's adjuvant. The mean association constants (K0s) of HEL-reactive antibodies (HEL-R-Abs) from each immunizing group to [3H]acetyl HEL or to [3H]acetyl-peptide were measured in solution by a double antibody method. Only peptide loop I.II (sequences 57-107 containing Cys64-Cys80 and Cys76-Cys94) induced high-affinity antibodies to HEL (K0 = 2.5 x 10(6)-2.3 x 10(7) M-1) among the three epitope peptides tested. The association constants of antipeptide loop I.II to [3H]acetyl peptide loop I.II were always one to two orders of magnitude higher than those to HEL. In addition, 50 to 80% of the anti-peptide loop I.II antibodies were reactive with native HEL. The specificity of anti-peptide loop I.II was directed to a conformational feature of the peptide rather than to native HEL and reactivity of the antibody to HEL was interpreted as a kind of cross-reaction. The HEL-R-Abs from anti-Ploop I.II antisera also manifested neutralizing activities against the enzymic activity of HEL when Micrococcus luteus was used as the substrate.

Animals↗
PubMed1992

Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat.

Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change.

Animals↗
PubMed1991

The effects of TFC-612, a 7-thia prostaglandin E1 derivative, on platelet function.

The anti-platelet activities of TFC-612, methyl 6-(((1R, 2S, 3R)-3-hydroxy-2-((1E, 3S, 5R)-3-hydroxy-5-methyl-1-nonenyl)-5- oxocyclopentyl) thio)hexanoate, were compared to prostaglandin E1 (PGE1). TFC-612 inhibited human, guinea-pig and rabbit platelet aggregation induced by ADP, collagen or epinephrine with potency 1-8 times that of PGE1. TFC-612 also inhibited thrombin induced (14C) serotonin release in rabbit platelets. Platelet aggregation was dose dependently inhibited 1 hr after oral administration of TFC-612 (0.32-1.0 mg/kg) and the inhibition lasted up to 6 and 24 hours at 0.32 and 1.0 mg/kg, respectively, in guinea-pigs. In contrast, PGE1 had no effect with oral administration at a dose of 3.2 mg/kg. TFC-612 (0.32-3.2 micrograms/kg, i.v.) induced platelet disaggregation of thrombi on Achilles tendon in the extracorporeal shunt model in cats. In addition, TFC-612 (1 mg/kg, po) inhibited the adhesiveness of guinea-pig platelets to a glass bead column ex vivo. TFC-612 increased cyclic AMP (cAMP) levels in rabbit platelets. Thus, the anti-platelet action of TFC-612 may be due to an increase in cAMP levels. These results indicate that TFC-612 might be an orally active anti-thrombotic drug.

Alprostadil↗
PubMed1991

The effects of TFC-612, a 7-THIA prostaglandin E1 derivative, on platelet function.

The anti-platelet activities of TFC-612, methyl 6-(( 1R,2S,3R)-3-hydroxy-2-((1E,3S,5R)-3-hydroxy-5-methyl-1-nonenyl)-5- oxocyclopentyl) thio)hexanoate, were compared to prostaglandin E1 (PGE1). TFC-612 inhibited human, guinea-pig and rabbit platelet aggregation induced by ADP, collagen or epinephrine with potency 1-8 times that of PGE1. TFC-612 also inhibited thrombin induced (14C) serotonin release in rabbit platelets. Platelet aggregation was dose dependently inhibited 1 hr after oral administration of TFC-612 (0.32-1.0 mg/kg) and the inhibition lasted up to 6 and 24 hours at 0.32 and 1.0 mg/kg, respectively, in guinea-pigs. In contrast, PGE1 had no effect with oral administration at a dose of 3.2 mg/kg. TFC-612 (0.32-3.2 micrograms/kg, iv) induced platelet disaggregation of thrombi on Achilles tendon in the extracorporeal shunt model in cats. In addition, TFC-612 (1 mg/kg, po) inhibited the adhesiveness of guinea-pig platelets to a glass bead column ex vivo. TFC-612 increased cyclic AMP (cAMP) levels in rabbit platelets. Thus, the anti-platelet action of TFC-612 may be due to an increase in cAMP levels. These results indicate that TFC-612 might be an orally active anti-thrombotic drug.

Administration, Oral↗
PubMed1991

Antifungal and antiviral activities of benanomicins and their analogues.

In vitro activities of benanomicins and their analogues against human immunodeficiency virus and fungi including Candida, Cryptococcus and Aspergillus, were examined. The free carboxyl group and at least one sugar moiety in the benanomicins were essential for their activities. Benanomicin A was most active and had low toxicity, and was selected as the best candidate for chemotherapy.

Animals↗
PubMed1991

Isolation of chicken-bek and a related gene; identification of structural variation in the ligand-binding domains of the FGF-receptor family.

cDNA clones carrying the chicken-bek gene and a related gene were isolated. Deducing the amino acid sequence of chicken-bek allowed us to predict that it encodes for a receptor tyrosine kinase related to the fibroblast growth factor (FGF) receptor, and that the chicken-bek gene and Cek3 are closely related. However, a significant structural difference was identified between chicken-bek and Cek3 within the putative extracellular region, in such a manner that the structure of the immunoglobulin-like domain was conserved. A probe specific to the altered structure detected mRNA in the tissues as did a probe common to bek and Cek3, indicating heterogeneity in the FGF-receptor family in a novel manner. Furthermore, another bek-like gene was isolated and the expressions of its mRNA and protein product were analysed in tissues and cultured cells.

Amino Acid Sequence↗
PubMed1990

Fiber-optic laser-Doppler anemometer microscope developed for the measurement of microvascular red cell velocity.

A fiber-optic laser-Doppler anemometer microscope (FLDAM) was developed and its applicability to the study of microvascular blood flow was examined by measuring red cell velocities in vivo and in vitro. The FLDAM consists of an intravital microscope equipped with a fringe-mode back-scatter LDA. A data processing method of the Doppler signal which used frequency averaging over the entire frequency range of the power spectrum was developed. Spatial resolution of the FLDAM varied from 17 to 200 microns with 50X to 5X objectives. In vitro experiments showed that the red cell velocity obtained by the FLDAM was equal to the mean flow velocity, within the accuracy of the measurements, for tube diameters from 35 to 100 microns, mean velocity from 0.7 to 17 mm/sec, and feed hematocrit of 20%, when 10X or 20X objectives were used. In vivo red cell velocity measurements conducted with the FLDAM in microvessels of rat mesentery with diameters from 6.5 to 49 microns showed that red cell velocities were about 1/1.6 times smaller than those obtained by the two-slit technique, which also suggests that the velocity obtained by the FLDAM corresponds to the mean flow velocity. This relationship was also established from theoretical considerations for the case where the FLDAM sampling volume covers the entire vessel cross section. Furthermore the frequency response of the FLDAM was established to be about 20 Hz, which was sufficient for measurement of pulsatile velocities in rat mesenteric microvessels.

Animals↗
PubMed1990

Kaposi's sarcoma: a light and electron microscopic study.

A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.

Aged↗
PubMed1990

Effects of cardiac assist on the bulk and regional mechanics of the ischemic left ventricle in dogs.

Pneumatically driven left ventricular assist devices (LVADs) were implanted between the left atria and the descending thoracic aortas of dogs and were counter-pulsated synchronously with the electrocardiogram at 1:1 and 2:1 duty ratios. Seven pairs of miniature sonomicrometers were implanted into the left ventricle (LV) to measure the LV muscular length and diameter. Ischemia was induced by the ligation of the left anterior descending coronary artery (LAD). Bulk and regional mechanical work were calculated from these dimensions and the left ventricular pressure. LVAD reduced the bulk work in the ischemic and normal hearts not only in the 1:1, but also in the 2:1, pumping modes. The left ventricular bulk work measured under the pump-off condition decreased progressively until around 2 h after the LAD ligation, and thereafter, it became constant. The regional myocardial work in the normal area of the ischemic heart was significantly decreased by the LVAD pumping (by 55%), whereas that in the ischemic area remained at near zero level regardless of pumping or nonpumping. The results obtained indicated that LVAD is useful not only to rest the severely damaged natural heart, but also to maintain the viability of ischemic myocardium.

Animals↗
PubMed1989

In vivo and in vitro measurements of red cell velocity under epifluorescence microscopy.

Studies of blood flow in mesentery, cremaster muscle, and small bore glass tubes were performed to obtain a relationship between mean velocity (Vmean) and red cell velocity using the two-slit method under epifluorescence (Vepi) and transillumination (Vtrans) microscopy. The velocities Vepi and Vtrans obtained in vivo for 47 measurements in arterioles and venules (12- to 51-micron internal diameter) were linearly related by Vepi = 0.83 Vtrans + 0.074, and the ratio Vepi/Vtrans decreased gradually with increasing vessel diameter (P less than or equal to 0.05). In vitro studies in tapered glass tubes (diameter 30-70 micron) were conducted for feed hematocrits (HF) from 10 to 40%. Under transillumination, Vtrans/Vmean was nearly constant with an average of 1.56 +/- 0.16 (SD) for all hematocrits and diameters. The velocity ratio, Vepi/Vmean, however, decreased with HF from 1.8 to 0.8 as HF was increased from 10 to 40%. Theoretical considerations suggest that the variations of Vepi/Vmean with tube hematocrit and diameter might result from attenuation of the excitation light by absorption and scattering by red cells, and also due to a finite depth of field of the microscopic objective.

Animals↗
PubMed1988

Effect of drive mode of left ventricular assist device on the left ventricular mechanics.

Pneumatically driven left ventricular assist devices (LVADs) were acutely implanted between the left atria and the descending aortas of dogs, and were driven in five pumping modes: electrocardiogram synchronous modes with the duty factors of 1:1, 2:1, and 4:1, and asynchronous modes with the pulse rates of 60 and 80 beats/min (bpm). The ventricular diameter and myocardial segment length were measured by an ultrasonic displacement meter and implantable miniature sensors. Bulk mechanical work of the left ventricle and regional mechanical work of the myocardium were calculated from these dimensions and the left ventricular pressure. LVAD reduced the bulk mechanical work of the left ventricle by 30-50% and the regional work by 30-60%. The mean aortic pressure and the total flow (= aortic flow + pump bypass flow) were highest in the 1:1 synchronous pumping mode, which indicates that this mode is most effective to maintain the systemic circulation and coronary blood flow. Asynchronous pumping and synchronous pumping with 2:1 duty factor were most useful to reduce the mechanical work of the left ventricle.

Animals↗
PubMed1986

Direct identification of phosphotyrosine-containing proteins in some retrovirus-transformed cells by use of anti-phosphotyrosine antibody.

For direct identification of phosphotyrosine-containing proteins in lysates of various cells, phosphotyrosine (P-Tyr) was coupled to carrier proteins and anti-P-Tyr antibodies were raised in rabbits and mice. The antibodies were highly specific for P-Tyr and did not cross-react with phosphoserine or phosphothreonine. The mean association constant of rabbit anti-P-Tyr antibody to N-acetyl-P-Tyr was about four times that of rabbit anti-azobenzene phosphonate antibody. In addition, anti-P-Tyr antibody scarcely cross-reacted with the 5'-monophosphate of ribosyladenine or the 5'-monophosphate of ribosylinosine, whereas anti-azobenzene phosphonate antibody cross-reacted appreciably with these compounds. Anti-P-Tyr antibody immunoprecipitated three oncogenic gene products from cells transformed with Rous sarcoma virus, Fujinami sarcoma virus, and Abelson murine leukemia virus, respectively. The immunoprecipitates with anti-P-Tyr antibody from cells transformed with these three retroviruses all manifested tyrosine kinase activity including activity for phosphorylations of oncogene products. In addition to the proteins reported previously, the following new phosphotyrosine-containing proteins were immunoprecipitated from the respective retrovirus-transformed cells by anti-P-Tyr antibody: Mr 230,000, 74,000, and 24,000 proteins (Rous sarcoma virus); Mr 230,000, 69,000, and 24,000 proteins (Fujinami sarcoma virus); and Mr 230,000, 62,000, and 54,000 proteins (Abelson murine leukemia virus).

Animals↗