Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 469 records · Page 26Linked to original sources

PubMed1990

Free Fatty acids regulate two galactosyltransferases in chloroplast envelope membranes isolated from spinach leaves.

Effects of MgCl(2) and free fatty acids (FFA) on galactolipid:galactolipid galactosyltransferase (GGGT) and UDP-galactose: 1,2-diacylglycerol galactosyltransferase (UDGT) in chloroplast envelope membranes isolated from spinach (Spinacia oleracea L.) leaves were examined. GGGT activity was sigmoidally stimulated by MgCl(2) with a saturated concentration of more than 5 millimolar. Free alpha-linolenic acid (18:3) caused a drastic increase in GGGT activity under limiting concentrations of MgCl(2), without affecting its maximum activity at higher MgCl(2) concentrations. Free 18:3 alone did not affect the GGGT activity. The effective species of FFA for the stimulation of GGGT activity in the presence of MgCl(2) were unsaturated 16- and 18-carbon fatty acids. GGGT activity was also stimulated by 18:3 in the presence of MnCl(2), CaCl(2) and a high concentration of KCl in place of MgCl(2). UDGT activity was hyperbolically enhanced by MgCl(2) with a saturated concentration of 1 to 2 millimolar. In contrast to GGGT, UDGT was severely inhibited by 18:3, and MgCl(2)-induced stimulation was completely abolished by 18:3. Unsaturated 16- and 18-carbon fatty acids were more inhibitory to UDGT than the saturated acids. The dependence of GGGT activity on monogalactosyldiacylglycerol (MGDG) and MgCl(2) concentrations was identical in the envelope membranes isolated from non- and ozone (0.5 microliter/liter)-fumigated spinach leaves, indicating that GGGT remained active in the leaves during ozone fumigation. The results are discussed in relation to the regulation of galactolipid biosynthesis by the endogenous FFA in the envelopes and to the involvement of GGGT in the triacylglycerol synthesis from MGDG in ozone-fumigated leaves.

Journal Article↗

PubMed1990

Expression of the alpha-chain gene in heterogeneous IgA immunodeficiency.

Five heterogeneous IgA-immunodeficient patients were analysed for expression of the alpha-chain gene. The number of surface IgA-bearing B cells was low in four patients. Southern blot analysis indicated no deletion of immunoglobulin structural genes coding for C alpha or alpha switching-region genes. The number of surface IgM and IgA double-bearing B cells increased in some patients. Addition of recombinant interleukin 4 (rIL-4), rIL-5, and rIL-6 to the normal B cells enhanced IgA production. However, B cells of the patients showed no or one-third lower IgA production in response to these lymphokines, even though there was proliferation. rIL-4, rIL-5, and rIL-6 induced low or no expression of alpha mRNA of the patients' B cells. These results suggested that the patients lacked B cells able to produce transcripts for the IgA heavy chain, and that some patients' B cells might be defective at the switch-recombination process from mu to alpha or from mu and alpha to alpha.

Adolescent↗

PubMed1990

Diabetes mellitus in a young man with Bloom's syndrome.

Bloom's syndrome (BS) is a rare autosomal recessive genetic disorder in which diabetes mellitus unusually frequently develops as a complication. We report on a 21-year-old Japanese male patient with BS who exhibited impaired glucose tolerance (IGT) in the initial oral glucose tolerance test (OGTT) and had developed patterns of diabetes mellitus by the second OGTT at the 2-years-and-2-months follow-up. German and Passarge reported that the onset of diabetes in patients with BS was in late adolescence or early adulthood. Our results support the findings of German and Passarge. Therefore, when a person with BS reaches late adolescence or early adulthood, an OGTT is necessary to ascertain whether the patient has IGT or diabetes mellitus as a complication, regardless of whether or not diabetic signs such as glucosuria are present.

Adult↗

PubMed1990

Electrical effects of okadaic acid extracted from black sponge on rabbit sinus node.

1. Effects of okadaic acid on electrical responses and spontaneous activity in the dominant pacemaker cells of rabbit sinus node were investigated by use of microelectrode techniques. 2. Okadaic acid (10(-5) M to 4 x 10(-5) M) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by increases in both maximum upstroke velocity at phase 0 (Vmax) and amplitude of action potential. 3. All of the effects of okadaic acid were relatively well preserved in a low-Ca2+ medium (0.12 mM). Okadaic acid restored the spontaneous activity of sinus node pacemaker cells even in a Ca2(+)-deficient medium. 4. The effects of okadaic acid were markedly inhibited or abolished in a low Na+ medium (24 mM or 70 mM) and in the presence of a slow channel blocking agent, verapamil (10(-6) M). 5. In voltage-clamp experiments using a two-microelectrode technique, okadaic acid (10(-5) M) caused an increase in the slow inward current without affecting the outward current. At a higher concentration (4 x 10(-5) M), the drug increased the outward current. 6. These results indicate that okadaic acid causes an increase in spontaneous activity of sinus node pacemaker cells mediated by an enhancement of slow inward current (Isi) through verapamil-sensitive Ca2+ channels.

Action Potentials↗

PubMed1990

Negative inotropic effects of disopyramide on guinea-pig papillary muscles.

1. The inhibitory effects of disopyramide on electromechanical responses were investigated in guinea-pig papillary muscles driven by electrical stimuli. Disopyramide up to 10(-5) M did not cause a negative inotropic effect, while the maximum upstroke velocity of the action potential (dV/dtmax) was significantly decreased. 2. At higher concentrations, this drug dose-dependently inhibited the contraction, and dV/dtmax was further decreased. This inhibition of contraction was accompanied by a depression of the slow action potential in partially depolarized preparations by increasing [K+]0 (26 mM). 3. In preparations pretreated with nifedipine (10(-6) M) and ryanodine (10(-6) M), the contraction was almost completely inhibited. In such preparations, ouabain (2 x 10(-6) M) markedly increased the contraction, probably through the Na(+)-Ca2+ exchange mechanism. This contraction was inhibited by disopyramide above 10(-8) M, and an almost complete inhibition was caused at 3 x 10(-5) M. 4. A similar inhibitory effect was observed on the contraction increased by the lowering of [Na+]0 (36 mM). 5. These results suggest that disopyramide at high concentrations inhibits Ca influx through slow Ca2+ channels and at low concentrations, it reduces the contraction increased through the Na(+)-Ca2+ exchange mechanism. Disopyramide had a greater effect on cardiac contractility mediated by the Na(+)-Ca2+ exchange mechanism.

Action Potentials↗

PubMed1990

Parameters that govern the regulation of immunoglobulin delta heavy-chain gene expression.

The mu and delta immunoglobulin heavy-chain genes comprise a complex transcriptional unit in which a single mRNA precursor gives rise to mu- and delta-specific transcripts. During the immature B-cell stage, posttranscriptional processing events involving alternate splicing and cleavage-polyadenylation site selection give rise to mu- but not delta-encoding transcripts. In terminally differentiated B cells, delta mRNA is not synthesized because of a transcription termination event occurring upstream of the delta-gene locus. In an attempt to gain insight into the respective contributions of alternate splicing and cleavage-polyadenylation in the control of delta mRNA synthesis, we have constructed a set of plasmids in which membrane mu (mu m)-delta intergenic sequences containing the mu m poly(A) site but differing in splicing capacity were inserted in between a VH and delta gene. The mu m-delta insertion vectors were transfected into a B lymphoma line representative of an immature stage, and proximal mu m poly(A) site usage and delta mRNA synthesis were assessed. To determine unequivocally whether the mu m-delta intergenic region can regulate termination, the insertion vectors were also transfected into a B myeloma line, and transcription through the region was measured. In immature B-cell transfectants, splicing site selection was found to have a key role in determining poly(A) site utilization and concomitant delta mRNA expression. Mature delta mRNA synthesis was blocked by an upstream cleavage-polyadenylation event only when the proximal poly(A) site was associated with appropriate splicing signals. Furthermore, in vitro transcription assays revealed that the mu m-delta intergenic region is sufficient to regulate transcription termination within a 1,2430-base-pair region containing the mu m poly(A) site in myeloma transfectants. The mu m-delta insertion vectors provide an excellent model system for studying the regulatory aspects of this transcription termination event.

B-Lymphocytes↗

PubMed1990

[Early changes in serum alpha-fetoprotein after chemotherapy in advanced testicular tumors].

The serum levels of alpha-fetoprotein (AFP) are known to undergo acute changes (paradoxical elevation) after effective chemotherapies for testicular germ cell tumors. In order to understand the clinical significance, the changes of the serum AFP levels after PVB therapy for testicular germ cell tumors were analyzed, and their relationship to the treatment effects was investigated in this retrospective study. Thirty-one patients with testicular germ cell tumors (11 with stage I, 7 with stage II, and 13 with stage III) which had been treated by PVB therapy were evaluated. The measurement of the serum AFP levels was performed by radioimmunoassay on Day 1 (the initiation day of the PVB therapy), thereafter on Day 8 and Day 22. The half-life (t1/2) or doubling time (t2) of the serum AFP were calculated. In patients with stage I disease, the serum AFP levels declined nearly according to its biological half-life between Day 1 and Day 22 after termination of chemotherapy (t1/2 = 6.2 days). In patients with stage II or III disease, the changes of the serum AFP levels were not consistent with the treatment results between Day 1 and Day 8. Namely, complete responders revealed a prolonged decline of the serum AFP levels (t1/2 = 63.0 days), partial responders a transient rise of the serum AFP levels (t2 = 49.5 days) and non-responders a sudden rise of the serum AFP levels (t2 = 9.9 days). On the contrary, the serum AFP levels changed in accordance with the treatment effects between Day 8 and Day 22. Early changes of the serum AFP levels were seen in patients with stage II or III disease between Day 1 and Day 8 after chemotherapy. It was indicated that the measurements of the serum AFP levels during this period were not useful for the evaluation of the treatment effects in these patients. Furthermore, it was suggested that the early changes of the serum AFP levels possibly correlate with the poor response. The mechanism of the early changes of the serum AFP was also discussed.

Adolescent↗

PubMed1990

[Echocardiography in patients with malignant metastatic neoplasms of the heart and great vessels].

Two-dimensional echocardiography was used to study malignant metastatic neoplasms of the heart and great vessels in 20 patients, 13 males and seven females, whose ages ranged from 15 to 72 years. Five patients had lung cancer; two each had breast cancer, malignant melanoma, hepatoma and one each had gastric cancer, urinary bladder cancer, adrenocortical carcinoma, malignant lymphoma, angiosarcoma, fibrosarcoma, leiomyosarcoma; and two had cancers with unknown primaries. Tumor invasion was demonstrated echocardiographically in the left atrium in one each with breast cancer, fibrosarcoma and gastric cancer; in the right atrium in two with hepatomas; in the right atrium and right ventricle in one patient with adrenocortical carcinoma; in the left ventricle in one with lung cancer; and in the pulmonary artery in one with malignant melanoma. Massive pericardial effusion was observed in 11 of 20 patients; two with pericardial tumors including malignant lymphoma and lung cancer. We conjectured that metastatic tumors in the right cardiac cavities came through the inferior vena cava, and other tumors in the left atrium, left ventricle and pericardium developed from direct extension of the primary lesions. There was an 80% mortality of the patients during the observation period, and the average survival period after the diagnosis of cardiac metastases was 5.5 months. However, one patient was still living after two years of radiation therapy and chemotherapy. Echocardiography proved a useful, non-invasive means for the detection and follow-up observation of metastatic cardiac tumors.

Adolescent↗

PubMed1990

[Pathologic diagnosis of renal transplantation].

Eighty-seven renal allografts were examined at our department between 1980 and 1989. In these specimens, 24 cases involved so-called "1 hour biopsy", including a case of donor carrying IgA nephropathy. Nine cases showed glomerulonephritis, of which three cases are suspected as de novo membranous nephropathy. Acute rejection, glomerular, tubular and vascular type were seen in 11 cases, and chronic rejection in 20 cases. Four cases showed tubular injury which may be associated with cyclosporine nephrotoxicity. At diagnosis of acute cellular rejection, immunohistological analysis was performed to characterize the composition of the micronuclear cells. In all cases we examined, T lymphocyte is dominant, and CD8+ (Leu 2) cells and CD4+ (Leu 3) cells were seen in various percentages. The Leu M1(+) macrophage was also seen in glomerular capillary lumen or peritubular space. Whether the expression of HLA-DR antigens is altered in renal transplants was examined. Expression of DR antigens increased considerably on renal tubular cells and glomerular capillary endothelial, and may be a markers of acute rejection.

Adult↗

PubMed1989

Rat cytotoxic T lymphocytes against human T-lymphotropic virus type 1-infected cells recognize gag gene and env gene encoded antigens.

T cell immune responses in syngeneic WKA/H rats were analyzed by using lymphoid cell lines, TARS-1, TART-1, and TARL-2, infected with human T-lymphotropic virus type 1 (HTLV-1). Spleen cells of rats in which these cell lines had been rejected were sensitized in vitro with the same cell lines, and cells cytotoxic to these HTLV-1+ cell lines, and cells cytotoxic to these HTLV-1+ cell lines were generated. The effector cells were CTL of the CD5+ CD8+ phenotype and showed restriction of MHC class I Ag. Direct tests as well as cold target cell inhibition tests with an array of cell populations showed that these CTL reacted only with syngeneic HTLV-1+ cell lines. When xenogeneic HTLV-1+ cell lines were similarly utilized for in vitro sensitization, rat CTL specific for syngeneic HTLV-1+ cells were generated. They were not, however, reactive with xenogeneic HTLV-1+ cells used for sensitization. Syngeneic rat cells selectively expressing gag, env, or pX gene coded Ag were prepared by infection of recombinant vaccinia viruses. In cold target cell inhibition tests of anti-HTLV-1 CTL with thus prepared cells, cytotoxicity against the syngeneic HTLV-1+ cells line, TARS-1, was inhibited by syngeneic cells expressing gag gene or env gene coded Ag. Inhibition was, however, more consistent and more dominant by cells with gag gene than those with env gene. Syngeneic cells with pX gene and MHC class I incompatible cells with gag, env, or pX gene did not inhibit cytotoxicity.

Animals↗

PubMed1989

Production of tumor necrosis factor-alpha by microglia and astrocytes in culture.

Stimulation of mouse astrocytes and microglia in enriched culture by lipopolysaccharide (LPS) results in the production of a cytotoxic factor that is functionally similar to macrophage-derived tumor necrosis factor-alpha (TNF). This cytotoxic factor kills murine L929 cells, and is neutralized by a monoclonal anti-mouse TNF. The production of this factor is inhibited by pretreatment of cells by actinomycin D. Microglia are more sensitive to LPS and produce much higher activity of cytotoxicity in lower concentration of LPS than astrocytes. These results suggest that microglia are the major producers of TNF in the brain and may play a role in certain pathological conditions in the brain.

Animals↗

PubMed1989

ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction.

HTLV-I transformed T cells not only express a large number of interleukin-2 receptors [IL-2R/p55(Tac)], but also produce a factor named ATL-derived factor (ADF) that augments the expression of IL-2R/p55(Tac). Based on a partial N-terminal amino acid sequence, complementary DNA (cDNA) clones for human and mouse ADF were isolated and sequenced. Recombinant ADF produced by COS-7 monkey kidney cells showed IL-2R/Tac inducing activity on YT cells, which are sensitive for ADF. ADF mRNA was strongly expressed in HTLV-I(+) T cells lines, but not in inactivated cells (THP-1, unstimulated PBMC). Furthermore, in normal human peripheral blood mononuclear cells, the expression of ADF mRNA was enhanced by mitogens or phorbol myristate acetate, suggesting a possible involvement of ADF in the lymphocyte activation. Homology analysis revealed an unexpected relationship between ADF and dithiol-reducing enzyme, thioredoxin, involved in many important biological reactions such as the conversion of ribonucleotides into deoxyribonucleotides, or the stabilization of glucocorticoid receptors. The biological significance of the generation of a redox potential in lymphocyte activation, and the possible involvement of dithiol reduction in the induction of IL-2R/Tac are discussed.

Amino Acid Sequence↗

PubMed1989

Effects of concanavalin A on cardiotonic responses to A23187 and isoprenaline.

Effects of the lectin concanavalin A on cardiotonic response to A23187 and isoprenaline were examined in guinea-pig papillary muscles driven at 0.2 Hz. Concanavalin A (Con A) alone did not affect the cardiac action potential and contractility at concentrations up to 3.6 x 10(-4) g/ml. The contraction increased by isoprenaline, beta-adrenoceptor agonist, was not significantly affected by Con A in this concentration range. However, the positive inotropic effect of A23187 (10(-6) M) was markedly inhibited by this lectin. The maximum inhibitory action was observed at 1.8 x 10(-4) g/ml, while below 3.6 x 10(-5) g/ml, Con A failed to inhibit the inotropic effect of A23187. The inhibitory effect of Con A (3.6 x 10(-4) g/ml) was observed only on the late component of biphasic contraction induced by A23187, and then A23187-induced prolongation of the action potential duration at an early repolarization phase (APD 10) also disappeared. Similar inhibitory action was caused by nifedipine (10(-6) M), but in contrast to Con A, nifedipine markedly inhibited the action potential plateau and the contraction by itself. In the presence of Con A, the residual inotropic effect of A23187 on the early component of contraction was blocked by ryanodine (2 x 10(-6) M). The present inhibitory effect of Con A was completely blocked by the pre-treatment with either alpha-methyl-D-mannoside (10 mM) or endoglycosidase F (1 mU/ml). Succinyl Con A (3.6 x 10(-4) g/ml) and wheat germ agglutinin (2.4 x 10(-4) g/ml) did not significantly affect the positive inotropic effect of A23187. In voltage clamp experiments, the slow inward current was markedly augmented by A23187. This augmentation was nearly completely inhibited by Con A. These results suggest that Con A prevents the process of activation of Ca channels by A23187 through the binding of this lectin to specific carbohydrate residues presumably resulting in cross-linking of glycoproteins on membrane surface. Con A-sensitive carbohydrate residue is assumed to be involved in the modulation of Ca channel activation by A23187.

Action Potentials↗

PubMed1989

Simple method for determination of A1c-type glycated hemoglobin(s) in rats using high performance liquid chromatography.

We have developed a new chromatographic method for the determination of rat glycated hemoglobins by cation exchange high-performance liquid chromatography. The hemoglobins were eluted by a two-step gradient, and the total assay time, including re-equilibration of the column, was 27 min. Two A1c type and one pre-A1c type rat glycated hemoglobins were separated and measured. The change in major HbA1c of rats, in which diabetes was induced by streptozotocin and which were subsequently treated with insulin, was monitored. In diabetic rats (n = 10, average blood glucose greater than 300 mg/dL), major HbA1c rose to 3.39 +/- 0.06% compared with controls (n = 10, 1.20 +/- 0.03%) during 5 wk. Insulin treatment decreased the HbA1c from 3.48 +/- 0.16% to 2.74 +/- 0.15% (p less than 0.01) in 6 wk. This method was also effective for the determination of mouse HbA1c.

Animals↗

PubMed1989

Calvin-Benson Cycle Enzymes in Guard-Cell Protoplasts from Vicia faba L: Implications for the Greater Utilization of Phosphoglycerate/Dihydroxyacetone Phosphate Shuttle between Chloroplasts and the Cytosol.

Activities of Calvin-Benson cycle enzymes were found in protoplasts of guard cells from Vicia faba L. The activities of NADP-glyceraldehyde-3-phosphate dehydrogenase (NADP-GAPD) and ribulose-1,5-bisphosphate carboxylase (RuBPC) were 2670 and 52 micromoles per milligrams chlorophyll per hour, respectively. Activities of NADP-GAPD and RuBPC in guard cells were increased by red light illumination, and the light activations were inhibited completely by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosystem II. Enzymes related to the Calvin-Benson cycle such as 3-phosphoglycerate kinase (PGAK), triose phosphate (TP) isomerase, and fructose-1,6-bisphosphatase (FBPase) were shown to be present in guard-cell chloroplasts. From these results, we conclude that the photosynthetic carbon reduction pathway is present in guard-cell chloroplasts of Vicia faba. We compared these enzyme activities in guard cells with those in mesophyll cells. The activities of NADP-GAPD and PGAK were more than several-fold higher and that of TP isomerase was much higher in guard-cell chloroplasts than in mesophyll chloroplasts. In contrast, activities of RuBPC and FBPase were estimated to be roughly half of those in mesophyll chloroplasts. High activities of PGAK, NAD-GAPD, and TP isomerase were found in fractions enriched in cytosol of guard cells. Illumination of guard-cell protoplasts with red light increased the cellular ATP/ADP ratio from 5 to 14. These results support the interpretation that guard cells utilize a shuttle system (e.g. phosphoglycerate [PGA]/dihydroxyacetone phosphate [DHAP] shuttle) for an indirect transfer of ATP and reducing equivalents from chloroplasts to the cytosol.

Journal Article↗

PubMed1989

Voltage-dependence of ryanodine-sensitive component of contraction in A23187- and isoprenaline-treated cardiac muscles.

1. The ryanodine-sensitive component (RSC) of contraction electrically induced in the presence of A23187 (10(-6) M) and isoprenaline (5 x 10(-8) M) was investigated in guinea-pig papillary muscles that had been partially depolarized to various membrane potentials by increasing [K+]o, and current and voltage clamp techniques. 2. Two components of contraction were produced by A23187 and isoprenaline at a stimulation frequency of 0.2 Hz. The early component was sensitive to ryanodine (10(-6) M) (corresponding to RSC), while the late component was sensitive to nifedipine (10(-6) M). 3. In the presence of nifedipine, RSCs produced by these drugs were selectively observed. Under these conditions, RSCs were voltage-dependently inhibited by a reduction in resting potential that was brought about by increasing [K+]o (10-26 mM). The onset of inhibition of RSCs appeared at a resting potential between -75 and -70 mV, and almost complete inhibition was observed at a potential between -55 and -50 mV, indicating that RSCs produced by these drugs have the same voltage-dependence. 4. In the absence of nifedipine, this voltage-dependent inhibition was also observed on the early component of contraction produced by A23187 without affecting the late component. 5. RSC produced by A23187 was not affected by blocking Na channel activation with tetrodotoxin (6 x 10(-6) M). 6. In current and voltage clamp experiments, this RSC was inhibited by reducing the resting and the holding potentials in much the same way as observed on the preparations depolarized by increasing [K+]o. Such dependence on voltage was not observed with either the slow action potential or the slow Ca inward current. 7. These results suggest that the dependence of RSC on resting potentials is not due to the changes in the fast Na and the slow Ca inward currents. The present RSC via ryanodine-sensitive internal Ca release may be mainly triggered by a mechanism different from Ca influx through slow channels.

Alkaloids↗

PubMed1989

Antinephritic effect of OKY-046, a thromboxane A synthetase inhibitor (1). Effects on crescentic-type anti-GBM nephritis in rats.

To induce crescentic-type anti-glomerular basement membrane (anti-GBM) nephritis, male Sprague-Dawley rats were immunized with rabbit gamma-globulin in Freund's complete adjuvant following i.v. injection of anti-GBM serum. At the same time, original type anti-GBM nephritis was induced in other rats by anti-GBM serum only. The animals with crescentic-type anti-GBM nephritis showed significantly higher platelet aggregability than that in rats with original-type anti-GBM nephritis at days 5, 10 and 40 after anti-GBM serum administration, respectively. To estimate the antinephritic effect of OKY-046, a thromboxane A synthetase inhibitor, it was given orally to rats at doses of 0.5, 2.5 or 20 mg/kg for 39 days after anti-GBM serum. OKY-046 (20 mg/kg) significantly inhibited the increase in both urinary protein and plasma cholesterol levels (40% and 35% vs. control, respectively). Moreover, when examined by light microscopy, this drug remarkably prevented histological involvement of the glomeruli. OKY-046 at 20 mg/kg had suppressed the hyperaggregability of platelets by 77% by day 40 as compared with the control, but doses of 0.5 and 2.5 mg/kg did not. It is concluded from these data that OKY-046 has beneficial effects on crescentic-type anti-GBM nephritis and may act through inhibition of not only platelet TxA2 but also glomerular TxA2 in its action to prevent histological alterations.

Acrylates↗

PubMed1989

Antinephritic effects of PGE1 and thiaprostaglandin E1, TEI-5178 and TEI-6122, on crescentic-type anti-GBM nephritis in rats.

The antinephritic effects of PGE1, TEI-5178 and TEI-6122 on crescentic-type anti-glomerular basement membrane (GBM) nephritis in rats were investigated. The test compounds were subcutaneously administered every day for 39 days after the injection of anti-GBM serum. PGE1 (2.0 mg/kg/day), TEI-5178 (0.25 or 0.5 mg/kg/day) and TEI-6122 (0.25 or 0.5 mg/kg/day) significantly reduced urinary protein by 30 to 50% of that of the control at the late stage of nephritis. These test compounds also suppressed the increase of blood urea nitrogen and the development of alteration in the glomeruli by the 40th day. Both TEI-5178 (0.5 mg/kg/day) and TEI-6122 (0.5 mg/kg/day) significantly suppressed the production of antibody to rabbit gamma-globulin in nephritic rats. This was not the case with PGE1, however. In additional experiments to clarify the antinephritic mechanisms of the test compounds, it was found that 15 min after one subcutaneous injection of PGE1 (1.0 mg/kg), TEI-5178 (0.5 mg/kg) or TEI-6122 (0.5 mg/kg), systolic blood pressure in the nephritic rats was transiently reduced by 50 to 60%. On the other hand, these test compounds augmented renal blood flow (20-50%) from 45 min after the injection. The relationship between the antinephritic effect and these subsequent findings will be discussed.

Alprostadil↗