Biomedical subjects

T Cornelius

Publications and source records attributed to T Cornelius.

11 recordsLinked to original sources

PubMed1997

The optimum pneumoperitoneum pressure for laparoscopic surgery in the rat model. A detailed cardiorespiratory study.

BACKGROUND: There is increasing interest in the rat model of laparoscopic surgery. This study evaluates the cardiorespiratory effects of increasing CO2 pneumoperitoneum (PP) in the rat. METHODS: Nine Sprague-Dawley rats were subjected to CO2 PP at pressures of 2, 5, 10, and 15 mmHg or control (no PP) under anesthesia. Catheters were placed in the femoral artery and the jugular vein to measure heart rate (HR), blood pressure (MAP), and arterial pH, PCO2, PO2, and HCO3. A thermistor probe in the aortic arch measured cardiac output (CO) and blood temperature (BT). RESULTS: CO2 PP had no effect on CO, MAP, or BT at any pressure. CO2 PP greater than 5 mmHg caused significant bradycardia and CO2 PP greater than 10 mmHg caused significant respiratory acidosis. CONCLUSIONS: CO2 PP pressures above 10 mmHg in rat should be avoided when performing laparoscopic surgery in the rat model.

Analysis of Variance↗

PubMed1997

Expression of immediate early genes after cardioplegic arrest and reperfusion.

BACKGROUND: Induction of protooncogenes such as c-fos, c-jun, and EGR-1 has been implicated in cellular growth and differentiation. Heat-shock proteins (HSPs) such as hsp 70 may mediate resistance to ischemia after heat shock and ischemic preconditioning. The effects of cardioplegia on the regulation of these immediate early genes are unclear. METHODS: Isolated rat hearts were subjected to different cold (5 degrees C) or normothermic (35 degrees C) cardioplegic solutions and reperfused with normothermic Krebs-Henseleit buffer. Right atrial biopsy specimens from patients undergoing coronary artery bypass grafting with cold cardioplegic arrest were taken before and after cardiopulmonary bypass. Analysis of immediate early gene messenger RNAs was performed using Northern blots. Related proteins were localized by immunohistochemistry. RESULTS: In rat hearts, cold cardioplegia for 40 minutes with Bretschneider or St. Thomas' II solution followed by 40 minutes' reperfusion resulted in a significant increase in left ventricular c-fos, EGR-1, and c-jun messenger RNA levels (4.0-, 3.1-, and 3.0-fold, respectively, with Bretschneider solution and 3.7-, 2.8-, and 2.1-fold, respectively, with St. Thomas' II solution) compared with control hearts perfused at 35 degrees C with Krebs-Henseleit buffer. Normothermic cardioplegia with St. Thomas' II solution was without effect, whereas sequential perfusion with Krebs-Henseleit buffer at 5 degrees C and 35 degrees C resulted in a similar increase in protooncogene messenger RNA levels. Only cold Bretschneider solution was related to a 5.2-fold induction of hsp 70 messenger RNA levels. Likewise, rat atrial tissues and samples from patients after cardiopulmonary bypass displayed a significant induction of these immediate early genes. Monoclonal antibodies against c-FOS and HSP 70 proteins stained nuclei and perinuclear spaces of endothelial cells and cardiac myocytes. CONCLUSIONS: Cold cardioplegic arrest and normothermic reperfusion are potent triggers for immediate early gene induction. Hypothermia emerged as the prime stimulus for the examined protooncogenes. In contrast, hsp 70 induction was dependent on the cardioplegic solution.

Animals↗

PubMed1997

Induction of early immediate genes and programmed cell death following cardioplegic arrest in human hearts.

OBJECTIVE: Under experimental conditions cardiac stress may induce early immediate genes. Of these, heat shock proteins like hsp 70 have been linked to preconditioning and cellular salvage. Protooncogenes like c-fos and c-jun act as transcription factors for other genes and may be involved in the regulation of programmed cell death. METHODS: Patients, 30, undergoing elective coronary artery bypass grafting, received either cold antegrade St. Thomas II or Bretschneider or Hamburg cardioplegic solutions with ten patients in each group. Tissue from right atria was removed before cardiopulmonary bypass and following cardioplegic arrest and reperfusion. Tissues were examined by Northern blots, immunohistochemistry, and in situ nick-end labeling of fragmented DNA as evidence for programmed cell death. RESULTS: There were no significant preoperative or operative differences between groups. Following cardioplegia and reperfusion, a significant induction of both protooncogene and heat shock protein 70 mRNA was observed. Whereas levels of hsp 70 were increased about two-fold in all groups (P < 0.05), induction of c-fos and c-jun was most pronounced following the Hamburg cardioplegic solution (P < 0.05 versus baseline and for differences to other groups). Induction on the protein level was confirmed using immunohistochemistry that furthermore, identified cardiac myocytes and endothelial cells being the cell types that expressed these genes. In contrast to prebypass samples, in situ nick-end labeling of fragmented DNA following cardioplegic arrest and reperfusion was positive, preponderately in subendocardial myocytes and endothelial cells. CONCLUSIONS: Cold cardioplegia is a potent stimulus for induction of the early immediate genes examined in human hearts. Increased expression of protooncogenes may be deleterious to cardiac myocytes as indicated by in situ nick-end labeling of DNA fragments. Differences in gene induction may add additional information for the evaluation of different cardioplegic strategies.

Aged↗

PubMed1997

Regulation of the rat atrial natriuretic peptide gene after acute imposition of left ventricular pressure overload.

The upregulation of left ventricular (LV) atrial natriuretic peptide (ANP) mRNA is a highly conserved marker of cardiac hypertrophy. The aim of this study was to further examine the pathway leading to ANP induction during pressure overload of the heart. Systolic wall stress was imposed acutely on isovolumetrically beating rat hearts in a Langendorff apparatus (sigma-=300 x 10[3] dyne/cm2). Northern and Western blots revealed that elevated wall stress induced LV c-fos and c-jun mRNAs (3.5- and 3-fold, P<.05 after 60 minutes), c-Fos and c-Jun proteins (3.9- and 4.3-fold, P<.05 after 120 minutes), as well as ANP mRNA (2.2-fold, P<.05 after 120 minutes). ANP upregulation was prevented by inhibition of protein synthesis (cycloheximide). Electrophoresis mobility shift assays were performed to link c-Fos and c-Jun (ie, components of the heterodimeric transcription factor AP-1) and ANP induction. A putative AP-1 binding site within the rat ANP promoter (nucleotides -512 to -473) bound specifically to nuclear proteins of wall stress-stimulated hearts. Antibodies directed against c-Fos protein resulted in a shift of this DNA/protein complex, suggesting physical interaction between AP-1 and the ANP promoter. Myocardial transfection of promoter constructs revealed that after acute imposition of wall stress, this AP-1 site enhanced a reporter gene (8- to 10-fold compared with a minimal promoter, P<.05). Interestingly, nuclear extracts of stimulated hearts as well as pure AP-1 protein bound to a putative CRE site (nucleotides -613 to -584) as well. Like the AP-1 site, this cAMP-responsible element (CRE) site was found to enhance the transfected ANP promoter/reporter gene significantly (17.5-fold, P<.05). Mutation of either AP-1 or CRE sites did not decrease reporter gene activity, whereas mutation of both resulted in loss of inducibility. These experiments suggest that LV ANP regulation after acute wall stress includes the activation of AP-1 and/or CRE cis acting elements. However, the transient nature of c-fos and c-jun upregulation also suggests that AP-1 is not the only mediator of ANP induction in LV hypertrophy.

Animals↗

PubMed1995

The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A-H2B and H3-H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (< 300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox, the 3' untranslated regions contain no poly A signal, but a palindromic sequence (3' palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A-H2B pair. The H1 upstream region contains the octameric promoter element GGTTGACC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intron-free. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II (66% identity). Organization of the core histone gene in pairs, and non-polyadenylation of mRNAs are features shared with animals, whereas peptide sequences and enhancer elements are shared with higher plants, assigning the volvocalean histone genes a position intermediate between animals and plants.

Amino Acid Sequence↗

PubMed1995

Angiotensin II-induced growth responses in isolated adult rat hearts. Evidence for load-independent induction of cardiac protein synthesis by angiotensin II.

Cardiac myocyte hypertrophy often occurs in response to both hemodynamic and neurohumoral factors. To study whether activation of the renin-angiotensin system by itself may induce a cardiac growth response, the acute effects of angiotensin II on cardiac protein synthesis were studied in isolated rat hearts. New protein synthesis in isolated buffer-perfused adult rat hearts was measured by incorporation of [3H]phenylalanine into cardiac proteins during a 3-hour perfusion protocol. Angiotensin II (1 x 10(-8) mol/L), administered alone or in combination with the alpha 1-blocker prazosin (1 x 10(-7) mol/L), stimulated protein synthesis in both ventricles. The rate of [3H]phenylalanine incorporation into cardiac proteins was 3.9-fold (P < .005) and 2.6-fold (P < .01) higher in angiotensin II-perfused (n = 6) than in vehicle-perfused (n = 6) left and right ventricles, respectively. The induction of new protein synthesis by angiotensin II was blocked by the angiotensin II type 1 (AT1) receptor antagonist losartan (1 x 10(-7) mol/L, n = 5). To study the pathways of angiotensin signal transduction, protein kinase C (PKC)-epsilon as well as cardiac c-fos and c-jun mRNA levels were analyzed. Angiotensin II (1 x 10(-8) mol/L, n = 20) resulted in a transient translocation of PKC-epsilon from the cytosol to the cellular membrane. However, compared with phorbol ester stimulation (phorbol 12-myristate 13-acetate [PMA], 1 x 10(-7) mol/L; n = 20), angiotensin II effects on PKC translocation were significantly less pronounced and required a more prolonged stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1990