Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure.     

Neuromagnetic localization using magnetic resonance images

Ionic flow associated with neural activation of the brain produces a magnetic field, called the neuromagnetic field, that can be measured outside the head using a highly sensitive superconducting quantum interference device (SQUID)-based neuromagnetometer. Under certain conditions, the sources producing the neuromagnetic field can be localized from a sampling of the neuromagnetic field. Neuromagnetic measurements alone, however, do not contain sufficient information to visualize brain structure. Thus, it is necessary to combine neuromagnetic localization with an anatomical imaging technique such as magnetic resonance imaging (MRI) to visualize both function and anatomy in vivo. Using experimentally measured human neuromagnetic fields and magnetic resonance images, the authors have developed a technique to register accurately these two modalities and have applied the registration procedure to portray the spatiotemporal distribution of neural activity evoked by auditory stimulation.     

Production of anti-erythrocyte antibodies by leukemic and nonleukemic B cells in chronic lymphocytic leukemia patients

We have assessed the specificity of antibodies from the leukemic B cells of five patients with both chronic lymphocytic leukemia and autoimmune hemolytic anemia (CLL-AHA). Leukemic cells from one patient displayed surface immunoglobulin with heavy and light chain isotypes identical to that of the patient's anti-red blood cell (RBC) antibodies, and the leukemic cells secreted antibodies in vitro with anti-RBC activity. However, in the remaining patients, the leukemic cells displayed surface immunoglobulin with light chain isotypes different from that of the patient's anti-RBC antibodies and secreted antibodies in vitro with no detectable anti-RBC activity. Thus, there are two distinct classes of CLL-AHA patients, differentiated by the presence or absence of an anti-RBC antibody-producing leukemic B cell clone. The apparent heterogeneity in the source of pathogenic anti-RBC antibodies may impact the treatment response of the two classes of CLL-AHA patients.     

Hospital staffing and hospital costs

A comparative study of costs per bed per day in teaching hospitals affiliated with Monash University compared with large non-teaching metropolitan hospitals (1964 to 1974) shows they are much higher in teaching hospitals. There is no evidence that this is due to the additional costs arising from the clinical schools. Research in the teaching hospitals and the accompanying high professional standards and demands on services are major factors accounting for the difference. Over the decade studied, the resident staff have increased by 77% and other salaried staff by 24%. The index of expenditure for the three teaching hospitals in the decade has increased by 386%.     

Microviscosity of togavirus membranes studied by fluorescence depolarization: influence of envelope proteins and the host cell

The microviscosities of the hydrophobic regions of the membranes of intact Semliki forest and Sindbis viruses grown on BHK-21 cells, of liposomes derived from the extracted viral lipids, and of protease-treated virions were measured by fluorescence depolorization using the fluorescence probe 1, 6-diphenyl-1,3,5-hexatriene. The intact virus membranes were found to have a higher microviscosity than did virus-derived liposomes, indicating the viral envelope proteins contribute to microviscosity. However, protease-treated virus, devoid of protruding spikes but with residual lipophilic peptide tails, was found to have a microviscosity more similar to that of the intact virus than to that of protein-free liposomes. Sindbis virus grown in BHK-21 cells at 37 C had a much higher microviscosity than did Sindbis virus grown on Aedes albopicuts cells at 22 C. Sindbis virus grwon in A. albopictus and BHK-21 cells also gave higher microviscosity values than did the intact host cells. These data indicate that both the virion proteins and the cellular lipids selected during viral growth and maturation contribute to the increased microviscosity of togavirus membranes.     

Pulmonary regurgitation in large atrial shunts without pulmonary hypertension

Seven patients with pulmonary regurgitation (PR), normal pulmonary artery (PA) pressures and large left-to-right atrial shunts are reported. Six had secundum atrial septal defects (ASD) and one had anomalous pulmonary venous drainage. These comprised 4% of 180 patients with atrial shunts and normal PA pressures. Pulmonary regurgitation was diagnosed clinically by mid-frequency diastolic decrescendo murmurs beginning after the pulmonic component of the second heart sound, and diagnoses were confirmed by catheterization. In two patients who had serial preoperative catheterizations over 8 and 16 years, PR progressed in one and was present only on the second study in the other. All patients underwent shunt correction, at which time the pulmonic anulus and artery appeared dilated, but the pulmonic valves were normal and did not require revision. In all patients the PR murmur disappeared after shunt correction alone, and on chest X-ray both PA and overall heart size decreased. Although it is known that pulmonary regurgitation occurs with atrial septal defects and pulmonary hypertension, the present study demonstrates that it also occurs with high flow atrial shunts, in which setting it has different implications and is reversible with shunt correction alone.     

Prevention of neonatal respiratory distress syndrome through the administration of prednisolone in the fetal period

The clinical effectiveness of antenatal prednisolone medication (prednisolone hemisuccinate) for the prophylaxis of idiopathic respiratory distress syndrome (IRDS) was studied in 114 premature infants with a gestational age between 28 and 36 weeks. There was a statistically significant difference (chi2 - test, p less than 0,01) between the frequency of IRDS in this group and in another one consisting of 137 premature babies with a nearly identical distribution of gestational age, whose mothers did not get prednisolone before delivery. It could be shown that the time interval between medical induction and delivery should not exceed 2 weeks, since the effect decreases with time. At present prednisolone medication during the fetal period may serve as useful prophylactic measure for IRDS in cases of premature birth. As there are a lot of contraindication against prednisolone and as we do know very much about side effects, it seems necessary to seek for other, less dangerous inductors.     

Abnormal tryptophan metabolism in a family with a history of bladder cancer

Tryptophan metabolism was studied in a family in which a sister and brother had bladder cancer. Urinary tryptophan metabolites after administration of 2 g L-tryptophan were measured in 4 sisters and 1 brother, all free of disease when studied. One sister with and 2 without histories of bladder cancer had significantly elevated levels of kynurenine, acetylkynurenine, and 3-hydroxykynurenine. Administration of 100 mg pyridoxine hydrochloride returned the tryptophan metabolism to normal in these 3 individuals. One brother with a 1 sister without bladder cancer had normal metabolism. A repeat study 2 years later confirmed the abnormal metabolism in the 3 sisters. Two sisters with abnormal tryptophan metabolism were given 200 mg L-kynurenine sulfate orally to bypass the effects of tryptophan oxygenase activity. Both excreted elevated levels of kynurenine and 1 excreted elevated levels of 3-hydroxykynurenine.