Variations of cardiac cycle length in patients with coronary heart disease before and after aortic coronary bypass surgery

It is well known that variations in cardiac cycle length or heart rates may be used for noninvasive evaluation of autonomic cardiovascular control. The investigation uses an original procedure. The data for analysis of cardiac cycle length variations (CCLV) are those obtained regularly at follow-up intervals, random 24-hour Holter 2-lead ECG recordings for 5 sec, and simultaneously calculated continuous sequence of mean heart rate. With the procedure, the correlations of CCLV with the parameters reflecting the early postoperative status of patients with CHD, including acute myocardial infarction, acute heart failure, rhythm and conduction disturbances, as well as age, operative stress, concurrent diseases. The findings are of both diagnostic and predictive value at subsequent stages of CHD treatment.     

Sialic acid-depleted red cells following acute myocardial infarction

A reduction of red cell SA in patients following acute myocardial infarction is reported and the effects of SA-depleted red cells on cardiac index and alveolar capillary blood flow in the dog are described. The mean red cell SA in 26 patients following acute myocardial infarction was 0.021 +/- 0.001 compared with a mean of 0.031 +/- 0.002 mumol./0.1 ml RBC in 12 normal subjects (p less than 0.01). In five dogs injected with neuraminidase, an enzyme which removes SA from the red cell membrane, a 43% decrease in mean cardiac index from 2.3 +/- 0.22 to 1.3 +/- 0.16 (p less than 0.01) occurred. In films of the pulmonary microcircuation the mean widths of typical alveolar capillary beds decreased 42.6% +/- 5% (p less than 0.01). In three other dogs, autotransfusion with SA-depleted stored blood resulted in a 25% decrease in mean cardiac index from 2.0 +/- 0.21 to 1.5 +/- 0.21 (p less than 0.2), and a 21.7% +/- 0.9% (p less than 0.01) decrease in mean widths of typical alveolar capillary beds. We conclude that a reduction of red cell SA follows acute myocardial infarction and that SA-depleted red cells decrease cardiac index and alveolar capillary blood flow in the dogs.     

Ultrastructural changes in articular cartilage in rheumatoid arthritis

Electron microscope studies of the articular cartilages removed in the course of the operation on 6 patients with rheumatoid arthritis were carried out. The processes of destruction of chondrocytes and the cartilaginous matrix in different regions of the articular cartilage were traced. In the surface areas of the drastically changed cartilage there were observed leucocytes of the synovial fluid, and in deeper areas--disintegration of chondrocytes and extracellular disposition of lysosomes and altered organellas, destroyed cartilaginous cells. In these areas destruction of collagenous fibres was particularly intensive. In areas of the tissue remote from the destuction hypertrophy of chondrocytes due to hyperplasia of various organellas and the Golgi complex in particular were noted. In the Golgi zone granules of glycogen were detected. No mitoses were observed. Apparently, the enzymatic destruction of the cartilaginous matrix in rheumatoid arthritis could proceed at the expense of the activazation of the synovial fluid lysosomes and lysosomes of chondrocytes themselves. A reparative regeneration of the disintegrating matrix was realized mainly because of hypertrophy of the functionally preserved chondrocytes.     

The use of monoclonal antibodies for detecting the influenza virus

The possibilities of using influenza A (Leningrad) 385/80 (H3N2) virus matrix protein-specific FITC-labeled D8 monoclonal antibodies in immunofluorescence assays were investigated. The virus antigen accumulation was detected in chorioallantoic cells of chick embryos. Exhibiting the type-specific properties, the fluorescent antibodies stain the perinuclear space, cytoplasmic membrane, and granular structures in the cytoplasm of infected cells. The haemagglutination test tires in the corresponding specimens were at least 1:16.     

Benzimidazole resistance in cyathostomes in horses in the Ukraine

The efficacy of treatment with cambendazole was tested in 1-year-old horses on a farm in Dubrovka, Ukraine. Thirty-five horses were treated. Their egg output was compared on the day of treatment and 14 days later with that of 33 untreated horses. Before treatment the mean number of eggs g-1 faeces was 614 in the controls and 766 in horses that had been treated. After 14 days the mean egg output in the controls was 580 and in the treated horses 369. This means a reduction of 54.5%. Only cyathostome larvae could be cultured from faeces collected after treatment. It can be concluded that benzimidazole resistance in cyathostomes is present in the Ukraine.     

The role of state policies and programs in buffering the effects of poverty on children's immunization receipt

OBJECTIVES: This study assessed the influence of public policies on the immunization status of 2-year old children in the United States. METHODS: Up-to-dateness for the primary immunization series was assessed in a national sample of 8100 children from the 1988 National Maternal and Infant Health Survey and its 1991 Longitudinal Follow-Up. RESULTS: Documented immunization rates of this sample were 33% for poor children and 44% for others. More widespread Medicated coverage was associated with greater likelihood of up-to-dateness among poor children. Up-to-dateness was more likely for poor children with public rather than private sources of routine pediatric care, but all children living in states where most immunizations were delivered in the public sector were less likely to be up to date. Poor children in state with partial vaccine replacement programs were less likely to be up to date than those in free-market purchase states. CONCLUSIONS: While state policies can enhance immunization delivery for poor children, heavy reliance on public sector immunization does not ensure timely receipt of vaccines. Public- and private-sector collaboration is necessary to protect children from vaccine-preventable diseases.     

Double mutant cycle analysis of aspartate 69, 97, and 103 to asparagine mutants in the m2 muscarinic acetylcholine receptor

Double mutant cycles provide a method for analyzing the effects of a mutation at a defined position in the protein structure on the properties of an amino acid at a second site. This approach was used to map potential interactions between aspartates 69, 97, and 103 in the m2 muscarinic acetylcholine receptor transmembrane helices 2 and 3. Receptors containing single and double aspartate to asparagine mutants were expressed in Chinese hamster ovary cells and their effects on ligand binding, signal transduction, and thermal stability determined. Analysis of the double mutant cycles showed that the mutations had approximately additive effects on ligand binding, signal transduction, and thermal stability. Ligand binding and thermal inactivation results support the conclusion that aspartate-103 is the ligand amine counterion. Effector coupling properties of the mutant receptors showed that aspartate-103 was also required for signal transduction activity. The mutation of aspartate-69 to asparagine completely eliminated signal transduction by the agonists acetylcholine, carbachol, and pilocarpine but not oxotremorine M, which caused reduced but significant inhibition of adenylyl cyclase and stimulation of phospholipase C. In contrast, adenylyl cyclase stimulation by the asparagine-69 mutant was elicited only by acetylcholine and carbachol but not by oxotremorine M. The variation in agonist-dependent effector coupling properties provides evidence that the asparagine-69 mutant can exist in activated receptor states that are different from the wild-type m2 muscarinic receptor.     

Interaction of divalent cadmium ions with nucleotides and native DNA

In normal embryos, mRNA encoding platelet-derived growth factor A (PDGF A) and the platelet-derived growth factor receptor alpha (PDGFR alpha) are found within and adjacent to the site of vertebral development, the sclerotome. These patterns of expression are consistent with PDGF action on the developing sclerotome and dermis. Homozygous Patch (Ph) mutant mouse embryos lack the receptor gene (Pdgfra) due to an extensive deletion at that locus. Consistent with the spatial pattern of Pdgfra expression, striking deformities are found in the spine and ribcage of Ph/Ph embryos. In particular, we show that late-gestation Ph/Ph embryos have occult spina bifida involving the entire spinal column. We have analyzed the progression of the axial defects in homozygous Patch embryos in detail. By late gestation it appears that the components of the vertebrae are present, yet the neural arches of the spine are misshapen. We propose that PDGF A is required for proper positioning of the neural arch condensation at all axial levels. Furthermore, since the neural tube appears to close normally, we suggest that spina bifida in the Ph homozygote is caused primarily by a somitic mesoderm abnormality rather than a neural tube defect.     

Application of hammerhead ribozymes for structural studies of ribosomal 5S RNAs

We evaluated the possibility that distinct proteolytic pathways contribute to the down-regulation of a novel (epsilon) or conventional (alpha) isoform of protein kinase C (PKC) in nonimmortalized human fibroblasts. Inhibitors of calpains and other cysteine proteinases, vesicle trafficking, or lysosomal proteolysis did not affect the down-regulation of PKC-alpha or -epsilon produced by bryostatin 1 (Bryo). Lactacystin (Lacta) and certain terminal aldehyde tripeptides or tetrapeptides, which selectively inhibit the proteasome, preserved substantial PKC-alpha and -epsilon protein from down-regulation by Bryo or phorbol-12-myristate-13-acetate. Lacta preserved active kinase in vivo, as shown by the retention of Bryo-induced autophosphorylated PKC-alpha. Concomitant with down-regulation, Bryo produced PKC-alpha and -epsilon species that were larger than the native proteins (80 and 90 kDa, respectively). Western blot analysis showed that the larger PKC-alpha species were ubiquitinylated. Treatment with Bryo plus Lacta synergistically increased multiubiquitinylated PKC-alpha, as expected if Bryo induces ubiquitinylation of PKC-alpha and Lacta blocks its degradation. Bryo also produced a 76-kDa, nonphosphorylated form of PKC-alpha and an 86-kDa form of PKC-epsilon. Phosphatase inhibitors decreased production of 76- and 86-kDa PKC-alpha and -epsilon by Bryo and preserved 80- and 90-kDa PKC-alpha and -epsilon, respectively. Our results suggest that the down-modulation of PKC-alpha and -epsilon occurs principally via the ubiquitin/ proteasome pathway. Dephosphorylation seems to predispose PKC to ubiquitinylation.