Myocellular injury induced by acute ischemia and subsequent reperfusion was studied in 38 dogs, with special reference to sarcolemmal permeability as determined by the vital ionic lanthanum (La3+) probe technique and electron microscopy. The left anterior descending coronary artery (LAD) was occluded in 14 dogs for 10 to 60 min, and the ischemic zone was perfused slowly for 7 min with a La(3+)-containing solution. In 21 dogs, the LAD was released for 10 min after occlusion and was then reperfused for 7 min with arterial blood plus the La(3+)-containing solution. Subsequently, in both groups of animals, the ischemic myocardium was subjected to perfusion fixation in preparation for electron microscopy. In normal cardiac myocytes, La3+ was localized exclusively in the extracellular space. After 10 to 20 min of ischemia, more than 80% of myocytes appeared normal or were damaged only slightly, and the majority continued to exclude La3+. After 10 min of ischemia, deposits of lanthanum were detected in 1 and 6% of myocytes in the absence or presence of reperfusion, respectively. The number of cells with such deposits was markedly increased after 30 min of ischemia (19%), as well as after 20 min of ischemia followed by reperfusion (17%), prior to the development of irreversible myocardial damage. After 60 min of ischemia with or without reperfusion, about 30% of myocytes showed severe injury with particulate deposits of lanthanum throughout the entire cell. These results indicate that sarcolemmal permeability increases during the early stage of myocardial injury due to ischemia or ischemia-reperfusion and contributes to the development of myocardial damage.

Animals↗

PubMedDate not supplied

Isolation of major histocompatibility complex class I cDNA from pink salmon (Oncorhynchus gorbuscha).

An MHC class I cDNA clone was isolated from pink salmon (Oncorhynchus gorbuscha). Eight amino acids, which have been shown in mammals to bind main-chain atoms of peptides, are well conserved in the salmon alpha 1 and alpha 2 domains. Nine amino acids in the alpha 3 domain are classified by Williams and Barclay (Ref. 1. Ann. Rev. Immunol. 6:381-405, 1988) as signature immunoglobulin superfamily residues. The pink salmon MHC class I extracellular domains show 84.2% amino acid identity with those of Atlantic salmon (Sasa p30). polymorphism of the MHC class I alpha 1 domain was determined using PCR with genomic DNA from 12 fish. Sixteen variants were identified with most diversity concentrated in those amino acids that bind directly to peptides in mammalian class I molecules. Non-synonymous substitutions predominate over synonymous ones in the codons encoding these polymorphic residues.

Amino Acid Sequence↗

PubMedDate not supplied

Early induction of anti-double-stranded DNA antibodies in lupus-prone MRL mice inoculated with Ly-24+ cells cloned from lymph node cells of an MRL/Mp-lpr/lpr mouse: possible effect of putative cytokines produced by cloned Ly-24+ cells.

We have reported that a cell line, KML1, obtained from lymph node cells of a 16-week-old female MRL/Mp-lpr/lpr (MRL/1) mouse produces a soluble factor(s) that promotes formation of anti-single-stranded (ss) DNA antibodies by cultures of spleen cells from old MRL/l mice (greater than 16 weeks old). Detailed examination revealed that KML1-7 cells cloned from the cell line KML1 were only positive for the Lys-24 (Pgp-1) phenotype, and were negative for other typical phenotypes tested, such as Thy-1, Ly-1, Ly-2, Ly-4 (L3T4) and Ly-5 (B220). This finding suggested that this line was of prothymocyte or myeloid cell lineage. From day 70 after subcutaneous inoculation of KML1-7 cells into 10-week-old MRL/Mp(-)+/+(MRL/n) mice, IgG anti-dsDNA antibodies began to replace IgM anti-dsDNA antibodies in the serum of these mice, but anticardiolipin, anti-trinitrophenyl hapten (TNP) and anti-poly(ADP-ribose) antibodies did not increase significantly. The predominant subclasses of anti-dsDNA antibodies that increased were IgG2a and IgG2b. IgG anti-dsDNA antibodies also became detectable as early as day 22 after inoculation of KML1-7 cells into MRL/l mice of 10 weeks old. The finding that in MRL/n mice the IgM isotype was increased first and was soon replaced by the IgG isotype was consistent with findings when spleen cells from MRL/n mice of 20 weeks old primed with ssDNA were cultured in the presence of conditioned medium containing a putative cytokine(s) (PC) produced by KML1-7 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Exercise-induced ST-segment changes permit prediction of improvement in left ventricular ischemic dysfunction after revascularization: evaluation with positron emission tomographic measurements of regional myocardial blood flow and cardiac output.

BACKGROUND: Prediction of the recovery of left ventricular (LV) ischemic dysfunction after revascularization is important in patients with coronary artery disease (CAD). We investigated whether the improvement in LV ischemic dysfunction after revascularization could be predicted preoperatively by exercise-induced ST-segment changes. METHODS AND RESULTS: Regional myocardial blood flow (RMBF) and cardiac output were measured with nitrogen 13-ammonia positron emission tomography at rest and during low-level exercise in 28 patients with angiographically proven CAD before and after successful revascularization and in 9 normal subjects. Before revascularization, exercise-induced upsloping ST-segment depression <1 mm 80 msec after the J-point was observed in 11 patients (group 1), horizontal depression of 1 to 1.5 mm was observed in 9 patients (group 2), and downsloping depression > or =1.5 mm was observed in 8 patients (group 3). The number of regions of critical CAD was greater in group 3 than in groups 1 and 2 (3.6 +/- 1.4 vs 1.6 +/- 0.7 and 2.2 +/- 1.1, p < 0.001, p < 0.02). Increase of RMBF in regions of critical CAD with exercise was lower in group 3 than in groups 1 and 2 (0.15 +/- 0.01 vs 0.22 +/- 0.01 and 0.18 +/- 0.02 ml/min per gram, p < 0.0001, p < 0.01). After revascularization, RMBF in regions of critical CAD both at rest and during exercise improved in groups 1 (0.49 +/- 0.15 to 0.60 +/- 0.18, 0.70 +/- 0.26 to 0.86 +/- 0.33 ml/min per gram, both p < 0.05) and 2 (0.50 +/- 0.15 to 0.62 +/- 0.19, 0.67 +/- 0.26 to 0.89 +/- 0.31 ml/min per gram, both p < 0.02), but was unchanged in group 3 (0.47 +/- 0.09 to 0.47 +/- 0.15, 0.62 +/- 0.17 to 0.64 +/- 0.23 ml/min per gram, both p = NS). Cardiac output at rest improved in groups 1 (4.98 +/- 0.43 to 5.35 +/- 0.50 L/min, p < 0.02) and 2 (5.08 +/- 0.52 to 5.53 +/- 0.28 L/min, p < 0.02), but was unchanged in group 3 (4.76 +/- 0.48 to 4.88 +/- 0.82 L/min, p = NS). CONCLUSIONS: Our results suggest that marked downsloping ST-segment depression induced by preoperative low-level exercise may predict a lack of improvement in LV ischemic dysfunction after revascularization.

Ammonia↗

PubMedDate not supplied

Transient uncrossed corticospinal fibres in the newborn rat.

A small number of uncrossed corticospinal fibres were demonstrated in a 1-day-old rat by injection of horseradish peroxidase into one hemisphere of the cerebral cortex. These fibres were not demonstrable after the age of 7 days.

Aging↗

PubMedDate not supplied

Transient retino-inferior collicular fibres in neonatal rats: their persistence after removal of one eye at birth.

Retinal projections to the inferior colliculus in the newborn albino rat were demonstrated by intraocular injection with horseradish peroxidase. During normal development, these retino-inferior collicular fibres disappeared by 26 days of age. However, after removal of one eye at birth, distinct retino-inferior collicular fibres arising from the remaining eye were preserved contralaterally in rats at 26 days of age.

Animals↗

PubMedDate not supplied

Monocyte chemotactic protein 1 amplifies serotonin-induced vascular smooth muscle cell proliferation.

Monocyte chemotactic protein 1 (MCP-1), which is synthesized by vascular cells, is a chemoattractant for monocytes and has been implicated in a wide range of acute and chronic inflammatory processes characterized by monocyte infiltration, including atherosclerosis. However, it is unclear whether MCP-1 is able to modulate vascular smooth muscle cell (VSMC) proliferation. We assessed the effect of MCP-1 on VSMC proliferation and its interaction with serotonin (5-HT), a mitogen for VSMCs. Growth-arrested VSMCs were stimulated with different concentrations of MCP-1 (25-200 ng/ml) and 5-HT (5 and 50 microM) in serum-free medium. DNA synthesis in VSMCs was measured by [3H]thymidine incorporation. 5-HT at concentrations of 5 and 50 microM significantly stimulated DNA synthesis by 1.8- and 2.1-fold over the control value, respectively (p < 0.0001). However, MCP-1 at the concentrations tested did not have any significant effect on DNA synthesis. Even though MCP-1 (50 ng/ml) by itself is not mitogenic, when added to 5-HT, it significantly amplified the mitogenic effect of 5-HT compared with that of 5-HT alone (p < 0.0001). The 5-HT2A receptor antagonist sarpogrelate (10 microM) and its major metabolite M-1 (0.1 microM), pertussis toxin (10 ng/ml), Src family protein tyrosine kinase (PTK) inhibitor PP2 (1 microM), protein kinase C (PKC) inhibitor Ro31-8220 (0.1 microM) and mitogen-activated protein kinase (MAPK) kinase inhibitor PD098059 (10 microM) significantly inhibited the mitogenic effect of 5-HT and its interaction with MCP-1. Anti-MCP-1 antibody (2 microg/ml) and the Janus kinase 2 (JAK2) inhibitor AG490 (10 microM) significantly inhibited the interaction of MCP-1 with 5-HT. Further, the amplified mitogenic effect of 5-HT with MCP-1 was completely reversed by the combined use of sarpogrelate with anti-MCP-1 antibody. Our results suggest that MCP-1 amplifies the mitogenic effect of 5-HT on VSMCs. The mitogenic effect of 5-HT may be mediated by the G protein-Src family PTK-PKC-MAPK pathway. The activation of the JAK2/signal transducer and activator of transcription 3 pathway by MCP-1 in addition to the MAPK pathway by 5-HT may explain the potentiating effect of MCP-1 on 5-HT-induced mitogenesis.

Animals↗