Detrimental effects after dobutamine infusion on rat left ventricular function: mechanical work and energetics

We have previously reported that continuous infusion of dobutamine into the coronary artery induces positive inotropic effects but induces no detrimental effects in cross-circulated, excised normal rat hearts and even in Ca2+ overload-induced contractile failing rat hearts. However, we hypothesized that some detrimental effects on left ventricular (LV) function are induced after continuous dobutamine infusion and the following clearance of blood dobutamine, as is the case after beta-adrenergic receptor stimulation. To test this hypothesis, we investigated LV mechanical work and energetics in the same type of preparations that underwent continuous dobutamine infusion and clearance of blood dobutamine. We found that both mean end-systolic pressure and systolic pressure-volume area (PVA; a measure of total mechanical energy per beat) at midrange LV volume were significantly (P < 0.01) decreased. The mean myocardial oxygen consumption per beat intercept, which is composed of for the total Ca2+ handling in excitation-contraction coupling and basal metabolism, of the and PVA linear relation was also significantly (P < 0.05) decreased (n=8). The mean slope of the linear relation was unchanged in such hearts. Post-dobutamine basal metabolism was unchanged (n = 5 of the 8 hearts). The moderate proteolysis of a cytoskeleton protein, alpha-fodrin was identified (n = 7 of the 8 hearts with the decreased intercept), after clearance of blood dobutamine. In agreement with our hypothesis, the detrimental effect of the post-beta-adrenergic receptor stimulation was induced by a moderate concentration of dobutamine; we found systolic dysfunction due to the impairment of Ca2+ handling in excitation-contraction coupling in the rat LV and proteolysis of a cytoskeleton protein, alpha-fodrin.     

Statistical analysis of the discharge patterns of medullary temperature-responsive neurones in rabbits.

To characterize the medullary temperature-responsive neurones in rabbits, statistical analysis of interspike intervals was performed on 24 neurones recorded at various temperatures of the medulla. It was found that the medullary neurone fired at a relatively regular interval and 11 of 24 neurones displayed an invariable precision in thermoreception over a broad range of medullary temperatures; also, that the temporal distribution of interspike intervals of medullary neurones was markedly different from that of hypothalamic neurones.     

Histamine downregulates CD14 expression via H2 receptors on human monocytes

Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.     

Simultaneous occurrence of medullary and follicular carcinoma in the same thyroid lobe

A rare case of the simultaneous development of medullary and follicular carcinoma of the thyroid gland in a 51-year-old Japanese woman is examined. A preoperative diagnosis was made by needle aspiration cytology. Neoplastic cells of the medullary carcinoma were positive for calcitonin and carcinoembryonic antigen, whereas the tumor cells of the follicular carcinoma were negative for these substances. This case presents evidence that, in rare cases, two malignant epithelial neoplasms of different origins can occur in the same lobe of the thyroid.     

Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18

Rat Kupffer cell (KC)-mediated cytotoxicity against both thesyngeneic hepatoma cell line AH70 and hepatocytes was evaluatedby changes in mitochondrial function, and the possible roleof ICAM-1/CD18 in the interaction between the cells was studied.Rhodamine 123 fluorescence, a marker of the mitochondrial membranepotential, decreased in AH70 cells after co-culture with KC,while that in hepatocytes was unchanged by co-culture. Thisdecrease was blocked by anti-ICAM-1, anti-CD18 and the Inhibitionof nitric oxide synthesis. Cytometric studies demonstrated thatICAM-1 expression on AH70 cells increased after addition ofIFN-, IL-1ß, tumor necrosis factor (TNF)- or KC, whilein hepatocytes ICAM-1 was not increased. Anti-ICAM-1 pretreatmentinhibited the increase in ICAM-1 expression and the decreasein rhodamine 123 fluorescence on AH70 cells after co-culturewith KC. CD18 on KC was increased only after co-culture withAH70. TNF- but not IFN- was detected in the supernatant of co-culturebetween KC and AH70 cells, and this production was partiallyinhibited by anti-ICAM-1 and anti-CD18. The activity of Induciblenitric oxide synthase in Kupffer cells and the levels of nitritesand nitrates in the co-culture supernatant increased over time,and this increase was attenuated either by addition of NO synthesisinhibitors, anti-ICAM-1 or anti-CD18. These results indicatethat the rat KC causes mitochondrial dysfunction in cancer cellsvia the production of NO and cell-to-cell adhesion via ICAM-1/CD18has an Important role in this cytotoxic process.     

Asymmetries of prefrontal cortex in human episodic memory: effects of transcranial magnetic stimulation on learning abstract patterns

Functional neuroimaging suggests asymmetries of memory encoding and retrieval in the prefrontal lobes, but different hypotheses have been presented concerning the nature of prefrontal hemispheric specialization. We studied an associative memory task involving pairs of Kanji (Chinese) pictographs and unfamiliar abstract patterns. Subjects were ten Japanese adults fluent in Kanji, so only the abstract patterns represented novel material. During encoding, transcranial magnetic stimulation (TMS) was applied over the left and right dorsolateral prefrontal cortex (DLPFC). A significant (P<0.05) reduction in subsequent recall of new associations was seen only with TMS over the right DLPFC. This result suggests that the right DLPFC contributes to encoding of visual-object associations, and is consistent with a material-specific rather than a process-specific model of mnemonic function in DLPFC.     

No allelic association between Parkinson's disease and dopamine D2, D3, and D4 receptor gene polymorphisms

Parkinson's disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson's disease. Genetic association studies between Parkinson's disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson's disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson's disease is associated with the dopamine receptor polymorphisms examined. © 1994 Wiley-Liss, Inc.     

An immunohistochemical study of bone morphogenetic protein in pleomorphic adenoma of the salivary gland

Bone morphogenetic protein (BMP) is a potent induction factor for new bone formation including heterotopic chondro-ossification in soft tissues. The immunohistochemical reaction for BMP was studied in 23 cases of pleomorphic adenoma of salivary gland by using a monoclonal antibody produced by hybridoma technique. Positive BMP immunoreactivity was seen in 87% of tumours. Immunohistochemical expression of BMP was observed in modified myoepithelial cells (88% cases), luminal tumour cells of tubulo-ductal structures (78% cases) and chondroid cells in hyaline tissue (22% cases). The authors concluded that the simultaneous presence of glycosaminoglycans as matrix substance and S-100 protein for calcium signalling are associated with BMP-mediated cellular activity of modified myoepithelial cells in the formation of chondroid structures in pleomorphic adenomas of the salivary glands.