Breakdown of blood pressure and body fluid homeostasis in heart transplant recipients

OBJECTIVES: This study was designed to investigate disturbances in arterial blood pressure and body fluid homeostasis in stable heart transplant recipients. BACKGROUND: Hypertension and fluid retention frequently complicate heart transplantation. METHODS: Blood pressure, renal and endocrine responses to acute volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant recipients receiving similar doses of cyclosporine (cyclosporine control group) and 7 normal volunteers (normal control subjects). After 3 days of a constant diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8 ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II, aldosterone, atrial natiuretic peptide and renin activity levels were determined before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at 2 and 4 h. Blood pressure, fluid balance hormones and renal function were monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in the two control groups but increased in the heart transplant recipients (+15 +/- 8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and urinary sodium excretion increased abruptly in the control groups sufficient to account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases were blunted (p < or = 0.05) and delayed in the heart transplant recipients, resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two control groups (p < or = 0.05) but not in the heart transplant recipients. Heart transplant recipients had elevated atrial natriuretic peptide levels at baseline (p < or = 0.05), but relative increases during the infusion were similar to those in both control groups. CONCLUSIONS: Blood pressure in heart transplant recipients is salt sensitive. These patients have a blunted diuretic and natriuretic response to volume expansion that may be mediated by a failure to reflexly suppress fluid regulatory hormones. These defects in blood pressure and fluid homeostasis were not seen in liver transplant recipients receiving cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may contribute to salt-sensitive hypertension and fluid retention in heart transplant recipients.     

Structural characterization of novel inositol phosphosphingolipids of Tritrichomonas foetus and Trichomonas vaginalis

Two major ethanolamine phosphate-substituted inositol phosphosphingolipids have been identified in the unsaponifiable acidic lipid fractions of Tritrichomonas foetus and Trichomonas vaginalis. The compounds were radiolabelled and purified by high-performance thin-layer chromatography followed by high-performance liquid chromatography. The structures were determined by a combination of tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR) experiments, and gas-liquid chromatography of components obtained by degradation and derivatization. Inositol in the T. foetus component was 1-linked to the phosphosphingolipid, had the phosphoethanolamine group at the 3-position and a fucosyl residue at the 4-position. The T. vaginalis component lacked the fucosyl moiety. Both organisms also produced inositol phosphosphingolipids having the same long-chain base (sphingosine or dihydrosphingosine) and the same fatty acyl distribution as the inositol diphosphate compounds. These glycosphingolipids may represent metabolic intermediates for new types of membrane anchors for surface glycopeptides or glycolipids that mediate the host-parasite relationship of these trichomonads. The MS/MS and NMR spectroscopic data should provide reference information for structural determinations of other phosphorylated inositol derivatives.     

Brainstem origin of preganglionic cardiac motoneurons in the muskrat

The muskrat, and aquatic rodent with a brisk and reliable diving response, shows a remarkable bradycardia after nasal stimulation. However, the medullary origin of cardiac preganglionic motoneurons is unknown in this species. We injected fat pads near the base of the heart of muskrats with a WGA-HRP solution to label retrogradely preganglionic parasympathetic neurons that project to the cardiac plexi. Results showed that the preponderance of labeled neurons was in ventrolateral parts of the medulla from 1.5 mm caudal to the obex to 2.0 mm rostral. Eighty-nine percent of the labeled neurons were located bilaterally in the external formation of the nucleus ambiguus, 5.6% were in the lateral extreme of the dorsal motor nucleus of the vagus nerve and 5.3% were found in the intermediate area in between these two nuclei. Although controversy still exists concerning the medullary origin of preganglionic cardiac motoneurons, our results from muskrats agree with those from most other species where preganglionic cardiac motoneurons were located just ventral to the nucleus ambiguus.     

Failure mode and effects analysis. An interdisciplinary way to analyze and reduce medication errors

The information model of systemic functions of the human brain reproduces important features of human intelligence: goal planning, prediction of needed results, behavior correction by feedback from the parameters of the results obtained and their comparison with the acceptor of action results. Human behavior imitation in the model is statistically proved by testing the model on a computer. An Adaptron apparatus based on the model quantitatively estimates the parameters of an important mechanism of the brain, namely human intuitive learning. With the Adaptron, the ade-dependent properties and some human intellectual dysfunctions are estimated, which reflect the mechanisms of prediction of future results, the building of memory traces in intuitive learning when the findings coincide with the planned results and the restructure of memory and respective behavior changes when the findings do not coincide with the planned ones.     

The role of ATM in DNA damage responses and cancer

Ataxia-telangiectasia (AT) is a complex, autosomal recessive disorder characterized by cerebellar ataxia, believed to result from progressive neurodegeneration, and telangiectasia, dilation of blood vessels within the eyes and parts of the facial region. AT patients suffer from recurrent infections caused by both cellular and humoral immune deficiencies and as a population, are significantly predisposed to cancer, particularly lymphomas and leukemias. Early attempts at treating these malignancies with radiotherapy revealed another hallmark of AT, a profound hypersensitivity to the cytotoxic effects of ionizing radiation (IR) which is recapitulated at the cellular level in culture. Predisposition to cancer and radiosensitivity observed in AT has been linked to chromosomal instability, abnormalities in genetic recombination, and defective signaling to programmed cell death and several cell cycle checkpoints activated by DNA damage. These earlier observations predicted that the gene defective in AT may encode a protein which plays a crucial role in sensing DNA damage and transducing signals that promote cell survival. Through the combined efforts of linkage analysis and positional cloning, a single gene was identified on chromosome 11q22-33 by Shiloh and colleagues and was found to be mutated in all four complementation groups previously characterized in cell lines derived from AT patients (Savitsky et al., 1995a,b). The predicted ATM gene product shows considerable homology to an emerging family of high molecular weight, phosphatidylinositol-3 kinase (PI-3 K)-related proteins involved in eukaryotic cell cycle control, DNA repair, and DNA recombination (Zakian, 1995). This landmark discovery has triggered a resurgence of biochemical and genetic studies focusing on ATM function which has brought forth insights regarding ATM activity and its role in DNA damage signaling.     

Aerobic repression of the Rhodobacter capsulatus bchC promoter involves cooperative interactions between CrtJ bound to neighboring palindromes

Previous studies demonstrated that bacteriochlorophyll, carotenoid, and light harvesting gene expression in Rhodobacter capsulatus is repressed under aerobic growth conditions by the repressor CrtJ. Isolated CrtJ is known to bind to the palindrome TGTN12ACA, which is present in two copies in the bchC promoter, one of which spans the -35 and the other the -10 sigma-70 recognition sequences. In this study, we demonstrate that CrtJ binds to the two palindromic sites in the bchC promoter in a cooperative manner. The level of cooperativity of CrtJ binding to the -35 palindrome was shown to be 26-fold. A distance of 8 base pairs between the two palindromic sites was shown to be critical for cooperative binding, as evidenced by the disruption of binding that resulted when +6 and +11 base pairs were inserted between the palindromes.