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The interaction between tobacco mosaic virus (TMV) and tobacco harbouring the N gene is a classical system for studying gene-for-gene interactions in disease resistance. The N gene confers resistance to TMV by mediating defence responses that function to limit viral replication and movement. We isolated the N gene and determined that N belongs to the nucleotide-binding-site-leucine-rich-repeat (NBS-LRR) class of plant disease resistance genes, and encodes both full-length and truncated proteins. Sequence homologies and mutagenesis studies indicated a signalling role for the N protein similar to that seen for proteins involved in defence responses in insects and mammals. The N gene confers resistance to TMV in transgenic tomato, demonstrating the use of the NBS-LRR class of disease resistance genes in engineering crop resistance. From the pathogen side of this interaction, the TMV 126 kDa replicase protein has been implicated as the avirulence factor that triggers N-mediated defence responses. We employed Agrobacterium-mediated expression strategies to demonstrate that expression of the putative helicase region of the replicase protein is sufficient to elicit N-mediated defences. The thermosensitivity of the N-mediated response to TMV is retained when induced by expression of this replicase fragment. Thus, both components of this gene-for-gene interaction are now available for studies that address the molecular mechanisms involved in N-mediated TMV resistance.

The bright yellow sponge Isodictya erinacea is one of several chemically defended sponges found on the benthos of McMurdo Sound, Antarctica. An investigation of the metabolites from this sponge has resulted in the isolation of purine and nucleoside metabolites, including the previously unreported erinacean (1) and p-hydroxybenzaldehyde. The latter metabolite has been demonstrated to cause a feeding deterrence behavior in Perknaster fuscus, the major predator of antarctic sponges.

A total of 19 steroids, of which 13 steroidal oligoglycosides (nine new and four known) and six polyhydroxylated steroids (four new and two known), has been isolated from the Antarctic starfish Acodontaster conspicuus. The mixture is dominated by glycosides composed of steroidal aglycons having the hydroxyl groups typically disposed on one side of the tetracyclic nucleus, i.e., 3 beta,4 beta,6 alpha,8,15 beta-, with some having a sulfate at C-6, and differing in the side chains and/or in the disaccharide moieties that are usually attached at C-26, with some at C-28 and C-29. Those compounds are accompanied by minute amounts of glycosides with a delta 8(14)-double bond in the steroid, which is a structural feature not previously found among polyhydroxysteroids derived from starfish. Small amounts of six related unglycosidated polyhydroxysteroids and three higher-molecular-weight asterosaponins complete the composition of the mixture. The structures of the new compounds were determined by interpretation of their spectral data and by comparison with spectral data of known compounds. Eighteen of these compounds were evaluated for their ability to inhibit growth in Antarctic marine bacteria isolated from either the water column or the surfaces of benthic marine invertebrates. Of these compounds, 50% were active against at least one Antarctic marine bacterium. This suggests that these compounds may play an important role in deterring microbial fouling.

A documentation tool designed for use by lactation consultants in the neonatal intensive-care unit provides an efficient and complete method for recording the progress of the mother and infant. It incorporates the research base into interventions that begin during the early postpartum period and continue through the preterm infant's hospital stay. The system for using this tool helps consultants in giving comprehensive and timely lactation support.

In an ongoing survey of the bioactive potential of microorganisms associated with marine invertebrates, the culture media of a sponge-associated bacterial strain of Pseudomonas aeruginosa was found to contain metabolites which inhibit the growth of several Gram-positive microorganisms. A series of diketopiperazines (1-6) including a new natural product (6) and two known phenazine alkaloid antibiotics (7 and 8) were isolated from the culture broth of this bacterium.

Plant breeders have used disease resistance genes (R genes) to control plant disease since the turn of the century. Molecular cloning of R genes that enable plants to resist a diverse range of pathogens has revealed that the proteins encoded by these genes have several features in common. These findings suggest that plants may have evolved common signal transduction mechanisms for the expression of resistance to a wide range of unrelated pathogens. Characterization of the molecular signals involved in pathogen recognition and of the molecular events that specify the expression of resistance may lead to novel strategies for plant disease control.

Atroxase, isolated from the venom of Crotalus atrox (western diamondback rattlesnake), is a nonhemorrhagic protease which has fibrinolytic activity in vivo. The primary structure of atroxase was deduced from the cDNA encoding the atroxase protein. The venom glands of Crotalus atrox were used to prepare a cDNA library. Degenerate oligonucleotides were synthesized based on the partial amino acid sequence of atroxase and were used as primers in the polymerase chain reaction to amplify overlapping cDNA fragments from the C. atrox cDNA library. The resulting cDNA fragments were subcloned, sequenced, and translated. The final nucleotide sequence shows high homology to previously described primary structures of nonhemorrhagic fibrinolytic proteases isolated from snake venom.

The complement component C4 genes of Old World primates exhibit a long/short dichotomous size variation, except that chimpanzee and gorilla only contain short C4 genes. In human it has been shown that the long C4 gene is attributed to the integration of an endogenous retrovirus, HERV-K(C4), into intron 9. This 6.36 kilobase retroviral element is absent in short C4 genes. Here it is shown that the homologous endogenous retrovirus, ERV-K(C4), is present precisely at the same position in the long C4 gene of orangutan and African green monkey. Determination of the short C4 gene intron 9 sequences from human, three apes, two Old World monkeys, and a New World monkey allowed the establishment of consistent phylogenetic trees for primates, which favors a chimpanzee-gorilla clade. The 5' long terminal repeats (LTR) and 3' LTR of ERV-K(C4) in long C4 genes of human, orangutan, and African green monkey have similar sequence divergence values of 9.1%-10.5%. These values are more than five-fold higher than the sequence divergence of the homologous intron 9 sequences between the long and short C4 genes in higher primates. The latter is probably a result of homogenization or concerted evolution. We suggest that the 5' LTR and 3' LTR of an endogenous retrovirus can serve as a reliable reference point or a molecular clock for studies of gene duplication and gene evolution. This is because the 5'/3' LTR sequences were identical at the time of retroviral integration and evolved independently of each other afterwards. Our data provides strong evidence for the short C4 gene being the ancestral form in primates, trans-species evolution, and the "slow-down" phenomenon of the sequence divergence in great apes.

Extracts of the dorid nudibranchTritoniella belli and stoloniferan coralClavularia frankliniana were chromatographed and analyzed by(1)H NMR and thin-layer chromatography. Three glycerol ethers were detected inT. belli, primarily 1-O-hexadecyl glycerol (chimyl alcohol). Chimyl alcohol was also detected after gradient flash chromatography and reverse-phase HPLC purification in the tissues ofC. frankliniana. The common omnivorous predatory Antarctic sea starOdontaster validus, a likely predator of benthic invertebrates, showed feeding deterrence to small cubes ofT. belli mantle tissue placed on the tube feet along the ambulacral feeding groove, while always extruding the cardiac stomach when presented with cubes of shrimp tissue of similar size. Filter-paper disks soaked in an aqueous shrimp solution and then dried were found to elicit a broad range of feeding behaviors inO. validus, including movement of the shrimp disk to the mouth, extrusion of the cardiac stomach, and the assumption of a humped feeding posture. Chimyl alcohol-treated shrimp disks caused significant feeding deterrence in sea stars when compared with control disks (solvent plus shrimp treated disks alone).T. belli andC. frankliniana appear to employ a defensive compound that has been found in a variety of temperate and tropical mollusks, where it has been demonstrated to deter fish predators. We provide evidence for further deterrent capabilities of chimyl alcohol and of its trophic relationship in the polar ecosystem of McMurdo Sound, Antarctica.

The common bright yellow antarctic lamellarian gastropodMarseniopsis mollis was examined for the presence of defensive chemistry. Proton nuclear magnetic resonance (NMR) spectroscopy indicated that a major component of ethanolic extracts purified by reversed-phase column chromatography was homarine. Further high-performance liquid chromatography (HPLC) analysis of the mantle, foot, and viscera verified the presence of homarine in all body tissues at concentrations ranging from 6 to 24 mg/g dry tissue. A conspicuous macroinvertebrate predator of the shallow antarctic benthos, the sea starOdontaster validus, always rejected live individuals ofM. mollis, while readily feeding on pieces of fish tail muscle. Filter paper disks treated with shrimp elicited a broad range of feeding behaviors in the sea starO. validus (movement of disc to mouth, extrusion of cardiac stomach, humped feeding posture). Shrimp disks treated with homarine (0.4 and 4 mg/disk) were rejected byO. validus significantly more frequently than control disks treated with solvent carrier and shrimp or shrimp alone. The highest concentration of homarine tested not only caused feeding deterrence, but in several sea stars a flight response was noted. Homarine was not detected in the tunic of the antarctic ascidianCnemidocarpa verrucosa, a presumed primary prey ofM. mollis. Nonetheless, crude extracts of the epizooites that foul the tunic (primarily the bryozoans and hydroids) contain homarine, suggestingM. mollis may ingest and derive its chemistry from these organisms. This appears to be only the third example of chemical defense in a member of the Order Mesogastropoda. As the vestigial internalized shell ofM. mollis is considered a primitive condition, the findings of this study lend support to the hypothesis that chemical defense evolved prior to shell loss in shell-less gastropods.

Telesto riisei, an octocoral from Hawaii, produces nineteen highly functionalized prostanoids, the punaglandins, which are characterized by various oxygenation at C-5, -6, -7, and -12, and a 10-chloro-9-cyclopentenone moiety. The absolute stereochemistry of the 10-chloroprostanoids is epimeric to that of the Pacific marine prostanoids without halogen. The punaglandins have shown anti-inflammatory and antitumor activity. A synthetic 10-thiomethyl derivative enhances in vivo mineralization in human osteoblasts.

Development of a blood-brain barrier (BBB) within mammalian CNS grafts, placed either intracerebrally or peripherally, has been controversial. Published data from this laboratory have emphasized the presence or the absence of a BBB within solid mammalian tissue or cell suspension grafts is determined intrinsically by the graft and not by the surrounding host parenchyma (e.g., brain, kidney, testis, etc.). Nevertheless, correctly interpreting whether or not a BBB exists within brain grafts is manifested by methodologies employed to answer the question and by ensuing neuropathological and immunological consequences of intracerebral grafting. The present study addresses these issues and suggests misinterpretation for the absence of a BBB in brain grafts can be attributed to: (1) rupture of interendothelial tight junctional complexes in vessels of CNS grafts fixed by perfusion of the host; (2) damage to host vessels and BBB during the intracerebral grafting procedure; (3) graft placement in proximity to inherently permeable vessels (e.g., CNS sites lying outside the BBB) supplying the subarachnoid space/pial surface and circumventricular organs such as the median eminence, area postrema, and choroid plexus; and (4) graft rejection associated with antigen presenting cells and the host immune response. The latter is prevalent in xenogeneic grafts and exists in allogeneic grafts with donor-host mismatch in the major and/or minor histocompatibility complex. CNS grafts between non-immunosuppressed outbred donor and host rats of the same strain (e.g., Sprague Dawley or Wistar rats) can be rejected by the host; these grafts exhibit populations of immunohistochemically identifiable major histocompatibility complex class I+ and class EE+ cells (microglia, macrophages, etc.) and CD4+ T-helper and CD8+ T-cytotoxic lymphocytes. PC12 cell suspension grafts placed within the CNS of non-immunosuppressed Sprague Dawley rats are rejected similarly. Donor cells from solid CNS grafts placed intracerebrally and stained immunohistochemically for donor major histocompatibility complex (MHC) class I expression are identified within the host spleen and lymph nodes; these donor MHC expressing cells may initiate the host immune response subsequent to the cells entering the general circulation through host cerebral vessels damaged during graft placement. Rapid healing of damaged cerebral vessels is stimulated with exogenously applied basic fibroblast growth factor, which may prove helpful in reducing the potential entry of donor cells to the host circulation. These results have implication clinically for the intracerebral grafting of human fetal CNS cell suspensions.

Hexane, chloroform, and methanol extracts of 18 species of antarctic sponges were tested for their ability to induce sustained tube-foot retraction in the antarctic spongivorous sea starPerknaster fuscus. Extracts were imbedded in silicone and used to coat the tip of a glass rod, which was allowed to contact an extended tube-foot. Retraction times were measured and compared with three controls: contact with a glass rod coated with a hexane extract of fish (feeding stimulant), contact with the glass rod alone (mechanical control), and contact with the glass rod coated with silicone alone (silicone control). Only extracts of the spongeMycale acerata did not elicit significantly longer tube-foot retraction times than controls for at least one of the three organic extracts. Hexane sponge extracts elicited the lowest levels of significant tube-foot responses, with only 39% of the sponge species tested showing activity in this fraction. In contrast, chloroform and methanol extracts elicited a significant tube-foot retraction response in 73% and 78% of the species tested, respectively. This indicates that in this assay repellent metabolites are generally more polar substances. It remains to be determined that secondary metabolites are responsible for all of the tube-foot retraction responses detected in sea stars exposed to sponge extracts; bioactive secondary metabolites have been isolated from a number of these antarctic sponges. It may be of ecological significance that the two rapidly growing sponges,Homaxinella balfourensis andMycale acerata, were either not repellent or had low repellency, and thatM. acerata is the primary dietary item ofPerknaster fuscus.

The human complement C4 genes in the HLA exhibit an unusual, dichotomous size polymorphism and a four-gene, modular variation involving novel gene RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin-like Gene X (RCCX). The C4 gene size dichotomy is mediated by an endogenous retrovirus, HERV-K(C4). Nearly identical sequences for this retrotransposon are present precisely at the same location in the long C4 genes from the tandem RCCX Module I and Module II. Specific nucleotide substitutions between the long and short C4 genes have been identified and used for diagnosis. Southern blot analyses revealed that HERV-K(C4) is present at more than 30 locations in the human genome, exhibits variations in the population, and its analogs exist in the genomes of Old World primates with species-specific patterns. Evidence of intrachromosomal recombination between the two long terminal repeats of HERV-K(C4) is found near the huntingtin locus on chromosome 4. It is possible that members of HERV-K(C4) are involved in genetic instabilities including the RCCX modules, and in protecting the host genome from retroviral attack through an antisense strategy.

We have established an efficient transposontagging system in Arabidopsis thaliana using the Activator/Dissociation (Ac/Ds) elements from maize. This system consists of two components, a stable trans-activator, Acst, that supplies transposase, and a cis-responsive Ds element. Ds and Acst were constructed with different selectable and screenable markers to facilitate monitoring of Ds excisions and insertions as well as segregation of Ds and Acst. Fusions of the 35S, rbcS, or CHS promoters to Ac transposase were used to trans-activate DsALS, a Ds element carrying an herbicide-resistance gene. The ALS gene encoding acetolactase synthase, which confers resistance to chlorsulfuron, functioned as a versatile marker for selection of plants grown in tissue culture as well as in soil. Thirty-five Acst lines were crossed to two DsALS lines, and the resulting progeny were assayed for germinal transposition of DsALS. Trans-activation of DsALS by Acst resulted in germinal excision frequencies of up to 64% when using 35S promoter-Ac transposase fusions, up to 67% when using rbcS-transposase fusions, and up to 1% when using CHS-transposase fusions. Amongst progeny bearing terminal excisions, Southern analysis revealed that 45% from 35S-Acst crosses and 29% from rbcS-Acst crosses carried reintegrated DsALS elements. The Ac/Ds system we have developed should prove to be an effective tool for stable gene tagging in Arabidopsis.

Recently two peptides consisting of amino acids (aa) 1 to 30 and 31 to 67 of the N-terminus of the 126 aa prohormone of atrial natriuretic factor (proANF), as well as atrial natriuretic factor (ANF, aa 99 to 126; C-terminus), were found to have vasodilatory and natriuretic properties. These peptides, as well as ANF, circulate in humans as part of the N-terminus of the prohormone. To determine the effect of graded exercise on the circulating concentrations of the N-terminus and C-terminus of the ANF prohormone in normal persons, 12 healthy individuals (mean age 45 +/- 2 years) were evaluated before, for 2 hours after, and during bicycle exercise at a work loads of 25, 50, 75, 100, 125, 150, and 175 W. Both the N- and C-terminus of the ANF prohormone were released simultaneously with graded exercise in direct proportion to the intensity of the work load, measured objectively via maximal oxygen consumption (VO2max), respiratory quotient, and heart rate. Both the N-terminus and C-terminus of the ANF prohormone had strong positive correlations (p less than 0.001) with blood pressure, heart rate, VO2max, and respiratory quotient. Following exercise, the C-terminus returned to preexercise levels within 30 minutes, while the N-terminus remained significantly elevated at 30 and 60 minutes postexercise, reflecting the longer half-life of the N-terminus in the circulation.

Deacetoxycephalosporin C hydroxylase from cell-free extracts of Streptomyces clavuligerus was stabilized partially and purified to near homogeneity by three anion-exchange chromatographies, ammonium sulfate fractionation, and two gel filtrations. The hydroxylase was a monomer with a Mr of 35,000-38,000. alpha-Ketoglutarate, ferrous iron, and molecular oxygen were required for the enzyme activity. The hydroxylase was optimally active between pH 7.0 and 7.4 in a 3-(N-morpholino)propanesulfonic acid buffer and at 29 degrees C. It was stimulated by a reducing agent, particularly dithiothreitol or reduced glutathione, and ATP. The requirement for ferrous ion was specific, and at least one sulfhydryl group was apparently essential for the enzymatic hydroxylation. The Km values of the hydroxylase for deacetoxycephalosporin C and alpha-ketoglutarate were 59 and 10 microM, respectively, and the Ka for ferrous ion was 20 microM. In addition to its known hydroxylation of deacetoxycephalosporin C to deacetylcephalosporin C, the hydroxylase catalyzed effectively an analogous hydroxylation of 3-exomethylenecephalosporin C to deacetoxycephalosporin C. Surprisingly, the hydroxylase also mediated slightly a novel ring-expansion of penicillin N to deacetoxycephalosporin C. The substrate specificity of the hydroxylase is overlapping with but distinguishable from that of deacetoxycephalosporin C synthase, the enzyme which normally mediates the ring-expansion reaction (Dotzlaf, J. E., and Yeh, W. K. (1989) J. Biol. Chem. 264, 10219-10227). Furthermore, the hydroxylase exhibited an extensive sequence similarity to the synthase. Thus, the two enzymes catalyzing the consecutive reactions for cephamycin C biosynthesis in S. clavuligerus represent apparent products from a divergent evolution.

Radionuclide ventriculography has become the standard method for serially evaluating left ventricular ejection fraction (EF). The "gold standard" for evaluating EF is the contrast ventriculogram, which uses mathematical models to arrive at the volumes used to calculate EF. These models are subject to possible error. This paper reports the standardization of volume measurements of a digital angiographic camera system using a series of cardiac phantoms and the correlation of measurement of the EF of a series of patients whose EF was determined by digital angiography and radionuclide ventriculography.

Effects of the ingestion of protein and carbohydrate conditioned a preference for one size of chow particle over another, which was triggered by need for a specific nutrient. This learned elicitation of nutrient-specific dietary selection was not changed by injection of dl-fenfluramine HCl (2.5 mg/kg). This indicates that previously observed effects of fenfluramine on differential intakes of dextrin- and casein-rich diets do not depend on nutrient-specific self-selection.

The effects of dl-fenfluramine (2.5 mg/kg) on selection between the textures of nutrient preparations were tested by presenting rats with a choice between pairs of three sizes of chow crumb with 45% dextrin, casein, maltodextrin, or calcium caseinate added or with no nutrient added. The usual effect of fenfluramine was to reduce the intake preference for a coarser over a finer crumb. This drug effect differed, however, with the preparation of protein or of carbohydrate added to each crumb size. There was no consistent effect of nutrient, and hence the reported effects of this dose of dl-fenfluramine cannot be attributed to nutrient-specific selection.

The incidence of cardiovascular death and myocardial infarction associated with ischemic heart disease has declined over the past 15 years. Whether this is associated with a decrease in the severity of coronary atherosclerosis is unknown. The extent of coronary atherosclerosis in men was determined by postmortem coronary angiography in 505 patients over an observation period of 14 years. Patients were divided into those with ischemic heart disease (42%) and those without (58%). Mean coronary scores showed no significant trends over the 14-year period in those without ischemic heart disease and for the last 10 years in those with ischemic heart disease. In those few patients evaluated early in the study with ischemic heart disease, a significantly lower coronary score was found compared to subsequent years. This study was performed during an era of declining cardiovascular death rates and a declining incidence of myocardial infarction, and suggests that this decline may relate to favorable changes in pathogenesis rather than to a decrease in extent of coronary atherosclerosis.

To investigate the tolerance and efficacy of moricizine HCl, single-blind placebo-controlled trials were conducted. The early protocols involved patients hospitalized for 14 days, and daily Holter monitoring was used to document efficacy and the degree of spontaneous variability of ventricular premature complexes (VPCs). Moricizine HCl was given orally from 2.9 to 15.3 mg/kg 3 times daily. Patients with lethal ventricular arrhythmias were excluded. Additional outpatient trials were conducted to define long-term efficacy and safety. A dose-response relation between moricizine HCl and the percentage of reduction in frequency of benign or potentially lethal ventricular arrhythmias was documented. Eighty-five percent of patients achieved a reduction in VPCs greater than 75% with daily dosages ranging from 10.1 to 15 mg/kg. This corresponded to a 95% decrease in mean frequency of VPCs. Long-term studies demonstrated no evidence of compromise in left ventricular function, and the proarrhythmic rate was only 2%. Symptomatic side effects were mild and usually well tolerated. Nausea, the most common, occurred in 11% of patients and dizziness in 9%. These results indicate that moricizine HCl is an effective and well-tolerated antiarrhythmic agent.

It has been documented that biogenic amines can stimulate Na+, K+-ATPase from various tissue preparations. However, it is unclear whether or not this stimulation occurs in myocardial tissues. We have evaluated possible catecholamine stimulation of purified Na+, K+- ATPase preparations utilizing a bovine ventricular microsomal preparation. We have studied the dose response of the enzyme to ouabain and digitoxigenin in the presence and absence of propranolol and norepinephrine. Our results indicate that propranolol increases the sensitivity of Na+, K+-ATPase to inhibition by digitalis, and that stimulation of Na+, K+-ATPase in bovine myocardium is not mediated via an adrenergic mechanism. In addition, our results indicate that in myocardial tissue, both stereoisomers of propranolol produce a direct nonspecific membrane effect which can modify Na+, K+-ATPase activity.

Cardiac chamber weight was determined at necropsy in 323 men to develop correlative studies of electrocardiographic criteria for ventricular hypertrophy. Thirty recommended criteria for left ventricular (LV) hypertrophy, 10 for right ventricular (RV) hypertrophy, and combinations of both criteria for combined hypertrophy were evaluated. Four methods for electrocardiographic diagnosis of LV hypertrophy were derived: (1) a modification of the Romhilt-Estes point system; (2) the presence of any 1 of 3 criteria: (a) S V1 + R V5 or V6 greater than 35 mm, (b) left atrial abnormality, or (c) intrinsicoid deflection in lead V5 or V6 greater than or equal to 0.05 second; (3) a combination of any 2 criteria or of 1 criterion (above) plus at least 1 of the following 3 additional criteria: (a) left-axis deviation greater than -30 degrees, (b) QRS duration greater than 0.09 second, or (c) T-wave inversion in lead V6 of 1 mm or more; and (4) the use of a single criterion--left atrial abnormality. Sensitivity varied from 57 to 66% and specificity from 85 to 93% among these 4 methods. Myocardial infarction increased sensitivity of the foregoing methods, but the specificity was reduced. Method 2 is preferred for the electrocardiographic diagnosis of LV hypertrophy. Two methods were useful for right ventricular (RV) hypertrophy: (1) the use of any 1 of 4 criteria: (a) R/S ratio in lead V5 or V6 less than or equal to 1; (b) S V5 or V6 greater than or equal to 7 mm; (c) right-axis deviation of more than +90 degrees, or (d) P pulmonale; and (2) use of any 2 combinations of the foregoing criteria. Sensitivity ranged from 18 to 43% and specificity from 83 to 95%. Combined hypertrophy was best diagnosed using left atrial abnormality as the sole criteria of LV hypertrophy, plus any 1 of 3 criteria of RV hypertrophy: (a) R/S ratio in lead V5 or V6 less than or equal to 1, (b) S V5 or V6 greater than or equal to 7 mm, or (c) right axis deviation greater than +90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Most measurements establishing standard values for the normal electrocardiogram have been derived from a healthy population, whereas many electrocardiographic interpretations are necessary in hospitalized or seriously ill patients. Therefore, the characteristics of the electrocardiogram were described from 48 autopsied men known to be free of cardiopulmonary disease by clinical assessment and by a special cardiac examination using postmortem coronary angiography and a chamber partition technique. Highest values, mean and standard deviation, and the upper 97.5 percentile or lower 2.5 percentile when appropriate were noted for QRS voltage, QRS axis and duration, and intrinsicoid deflection in V5 or V6. Any ST-segment and T-wave changes were noted as well as left and right atrial abnormalities. Twenty-eight electrocardiographic criteria recommended to detect left ventricular hypertrophy and 10 recommended to detect right ventricular hypertrophy were evaluated for percentage of false-positive results and the 97.5 percentile value for each criterion was developed from the present data base. The data in this study can be used as a standard for comparing electrocardiographic variation in middle-aged men with specific relevance for electrocardiographic criteria of ventricular hypertrophy.

To compare the effects of different transformation methods on the integration behavior and structural stability of integrated foreign genes in plant cells, tobacco protoplasts were transformed with Escherichia coli plasmid pLGV2103neo DNA using the Ca phosphate DNA coprecipitation technique. Parallel transformations were done by cocultivation with Agrobacterium tumefaciens harboring the Ti plasmid derivatives pGV3850::2103neo or pGV3850::1103neo. A comparison of the fine structure of the integrated donor DNA obtained by direct gene transfer and by cocultivation indicates that the donor DNA in cells transformed by the former technique undergoes structural changes and concatemerizations, while the DNA integrated by the latter procedure is often unaltered. The cotransformed nopaline synthase gene, which is present in the donor Ti plasmid DNA, was inactivated in two out of nine cases. Once integrated, the arrays of selectable marker DNA appear to be structurally stable under different cell culture and selection conditions, as well as after genetic transmission.

The effects of concurrent disopyramide phosphate and quinidine sulfate therapy were studied in 16 normal healthy adults. No adverse effects serious enough to warrant discontinuation of therapy were observed. There was a small but significant increase in disopyramide serum concentration when concurrent quinidine therapy was given and a small decrease in quinidine serum concentration when disopyramide was added. No significant change in elimination half-life was seen for either drug. Both drugs produced prolongation of the corrected QT interval. This QT prolongation was greater for quinidine than for disopyramide.

This study investigated nursing staff attitudes toward the geriatric nurse practitioner as an agent of change in a long-term care facility, based on two University of Miami GNP students' practicum in a county nursing home. Nursing personnel were surveyed before and after the practicum to measure their acceptance of the GNP. While nursing staff initially held a wait-and-see attitude, posttest ratings were favorable. Recommendations for improving quality of care in the setting were made by student participants, and a six-month follow-up revealed that a number of changes had been implemented.

M-mode echocardiographic right ventricular wall thickness (RVW) and diastolic right ventricular internal diameter (RVID), when above the accepted normal range (RVW less than or equal to 5 mm, RVID less than or equal to 26 mm), are frequently used clinically to predict the presence of right ventricular hypertrophy. RVID was compared to anatomic right ventricular mass (RVM) in 27 patients and to RVW in 13 patients to determine their accuracy for predicting right ventricular hypertrophy (RVM greater than 65 gm). When increased, both measurements were specific for right ventricular hypertrophy. The specificity for RVW above 5 mm was 100% and for RVID greater than 26 mm was 79%. Neither was a sensitive indicator of hypertrophy. Only 36% of those with anatomic right ventricular hypertrophy had an echocardiographically dilated ventricle, and 67% had a thickened free wall. Neither measurement proved to be an accurate predictor of RVM, with a correlation for RVW of 0.56 and for diastolic RVID of 0.19.

The sensitivity of 30 electrocardiographic criteria for left ventricular (LV) hypertrophy, isolated or combined, was examined to determine the relation to the underlying disease. Patients with coronary artery disease (CAD), systemic hypertension, valvular heart disease and cardiomyopathy were evaluated. A cardiac partition technique was used to define ventricular hypertrophy. Single electrocardiographic criteria often showed high sensitivity for 1 disease state, but not for others. Precordial voltage criteria were most sensitive for those with hypertensive and valvular disease. A QRS axis of more than -30 degrees occurred most often in patients with CAD. Both left atrial abnormality and abnormal T-wave inversion of more than 1 mm in V6 occurred with a high sensitivity in general; however, T-wave inversion of more than 1 mm in V6 had a low sensitivity in cardiomyopathy. Methods using combinations of various electrocardiographic criteria improved sensitivity. Using these methods, sensitivity of the electrocardiogram for LV hypertrophy was excellent for patients with systemic hypertension and valvular heart disease and acceptable by usual standards for patients with CAD and cardiomyopathy. Because the use of a single criterion is often ineffective, methods using multiple electrocardiographic criteria to detect LV hypertrophy are recommended when the patients under study have diverse cardiac diseases.

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531 +/- 25, 371 +/- 18, and 22 +/- 1 fmol/ml (+/- SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10- to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increased proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.

A double-blind, randomized study was designed to evaluate the efficacy of oral propafenone and oral quinidine in suppressing premature ventricular complexes (PVCs). Twenty-five men were studied for 3 weeks. Twelve were randomized to the quinidine group and 13 to the propafenone group. Small doses of the drugs were administered for 1 week (200 mg of quinidine every 6 hours or 300 mg of propafenone every 12 hours) and large doses were administered for another week (400 mg of quinidine every 6 hours or 300 mg of propafenone every 8 hours). Strict criteria were used to define responders to antiarrhythmic therapy. For more than 85% reduction in total PVCs per hour: During the low-dose week, 36% in the quinidine group and 50% in the propafenone group were responders (difference not significant [NS]), while during the high-dose week 33% and 64% were responders (NS). For more than 95% reduction of ventricular couplets per hour: During the low-dose week, 45% in each group were responders, while during the high-dose week, 56% and 60% were responders (NS). For 100% abolition of ventricular tachycardia (VT) beats per 24 hours: During the low-dose week, 60% in the quinidine group and 56% in the propafenone group were responders (NS); during the high-dose week 80% and 67% were responders (NS). There was no significant difference in the 2 groups in incidence of side effects. This study shows comparable efficacy and tolerance of propafenone and quinidine for the control of ventricular arrhythmias in ambulatory patients with diverse forms of heart diseases.

Freely feeding rats received an anorexigenic dose of dl-fenfluramine HCl (5 mg/kg). Two hours following injection, their stomachs retained significantly greater dry weight contents than saline-injected controls. The same dose of fenfluramine decreased the rate of gastric emptying over a 2 h period to a similar extent in mildly food-deprived rats. The peripherally acting serotonin antagonist xylamidine counteracted the effect of fenfluramine in prolonging the satiating effect of an ad libitum meal of a given size. We propose therefore that the principal mechanism by which fenfluramine reduces food consumption in freely feeding rats is through a prolongation of the satiating effect of absorption as a result of slowing of gastric emptying, presumably via enhanced release of serotonin from nerve terminals in the wall of the gastrointestinal tract.

Although the left ventricle is traditionally viewed as the heart's main pumping chamber, no correlation has been shown between left ventricular (LV) ejection fraction (EF) at rest and exercise capacity in patients with chronic LV failure. Because vasodilators with venodilating activity increase exercise capacity more than predominant arterial dilators in patients with LV failure, right ventricular (RV) function may relate to exercise capacity in these patients. In 25 patients with chronic LV failure, caused by coronary artery disease in 12 patients and idiopathic dilated cardiomyopathy in 13 patients, RVEF and LVEF at rest were measured by radionuclide angiography. Maximal upright bicycle exercise testing was also performed to determine maximal oxygen consumption, which averaged only 13 +/- 4 ml/min/kg. The LVEF at rest was 26 +/- 10% and did not correlate with maximal oxygen consumption (r = 0.08). However, the RVEF was 41 +/- 12% and correlated with maximal oxygen consumption (r = 0.70, p less than 0.001) in the same patients. The correlation was stronger (r = 0.88) in patients with coronary artery disease than in those with idiopathic dilated cardiomyopathy (r = 0.60). Thus, RVEF at rest is more predictive of exercise capacity than LVEF in the same patients with chronic LV failure. These results are consistent with the clinical observation that only venodilating agents increase exercise capacity of patients with chronic LV failure.

The importance of the once-obscure right ventricle is becoming evident. Even in disorders that primarily affect the left ventricle, the once-considered-passive conduit has proved essential for maintenance of normal cardiac output. In coronary artery disease, the function of the right ventricle is affected by both its circulation and the after-load placed on it by dysfunction of the left ventricle. In congestive heart failure, right ventricular function relates to functional capacity, whereas left ventricular function does not, and right ventricular ejection fraction is a useful prognostic guide in these patients. In mitral and aortic valvular disease, the role of the right ventricle is only now becoming evident, and the precise interplay of all factors has yet to be explained. In systemic hypertension, it is likely that the pulmonary circulation is affected by the same humoral factors that elevate systemic pressures.

Left atrial (LA) abnormality determined from precordial lead V1 was assessed by 2 observers as a criterion of left ventricular (LV) hypertrophy in the presence of right bundle branch block (BBB) in 23 patients. The presence of LV hypertrophy was confirmed from a postmortem cardiac partition technique and defined at 2 levels of confidence: probable and definite hypertrophy. Observers reliably differentiated between the hypertrophied and normal-sized ventricle in the presence of right BBB by using LA abnormality as an electrocardiographic criterion. When defined as definite hypertrophy, observer 1 correctly identified LV hypertrophy in 78% of the cases and observer 2 in 67% of the cases. False-positive results were present in 21% of cases by observer 1 and 14% by observer 2. Comparable results were achieved when a definition of probable hypertrophy was used. Observer performance of recognition of LA abnormality in this study was satisfactory with 91% agreement between observers. Our results are comparable and in some instances superior to conventional criteria commonly recommended to diagnose LV hypertrophy on the electrocardiogram without right BBB.

Thirty-two men with chronic ventricular arrhythmias responded to propafenone, a new potent antiarrhythmic agent, in short-term trials with 85% or greater reduction of total ventricular premature complexes (VPCs) per hour, 95% or greater reduction of ventricular couplets (VCs) per hour, and 100% abolition of ventricular tachycardia (VT) beats per 24 hours. These patients were continued on long-term propafenone therapy to assess sustained therapeutic efficacy and safety. Thirty patients completed 1 year and 26 patients completed 2 years of testing with this agent; one patient died of sudden death and another died of a noncardiac cause. Although there were significantly fewer patient responders at 1 and 2 years, the majority of patients (greater than 79%) continued to respond optimally to propafenone. Side effects were minor and included bitter taste, dizziness, congestive heart failure, fatigue, and significant prolongation of the PR and QRS intervals. Propafenone has sustained antiarrhythmic efficacy after 2 years without serious toxicity.

San Antonio, Tex, has a long history of having a high rate of tuberculosis, but from 1960 through 1984, the rate was reduced by 82.6%. In 1984 it had a lower case rate than all but one of the six major Texas cities. The rate reduction involved all ethnic groups. The City Chest Clinic treats most of the new active cases, either by providing all necessary services or by supplying medication in cooperation with local physicians. The use of chemotherapeutic drugs has greatly reduced the transmission of the disease. Preventive therapy may prevent infection or reduce the bacterial population in contacts of active cases. The city health department's nursing division provides follow-up of patients and contacts. To prevent premature discontinuation of medications, nurses observe selected patients as they take their medicines. High case rates among minority ethnic groups, although improved, still are observed. Furthermore, high rates of new active cases are still found in areas of the city with the lowest median family income, low median values of homes, and overcrowding.

Mildly food-deprived rats were presented at the same time either high- and low-carbohydrate diets or protein-containing and nonnutritive diets differing in flavor in parallel with nutrient composition. After a few days of these concurrent 10-minute presentations, the rats preferred the flavor of the richer or nutritive diet. Such preference conditioning also occurred when there was a 10-minute delay between the presentation of two flavors in nonnutritive diet and intubation of a mixture of nutrients in proportion to the flavor intakes. Thus, rats are able to perceive the difference between the nutritional aftereffects of two distinctive diets presented concurrently and to learn to respond differentially to associated flavors even when there was a delay as long as that used in earlier studies with pyloric closure. Therefore, the reinforcement that has been suggested to arise from gastric chemoreception can be attributed instead to delayed postgastric effects.

We believe that nurse practitioner role mastery should occur through supplementation of former roles, beginning early and continuing throughout the entire educational process, rather than through realignment to a new role. The educational process should therefore enable the student to identify with and build upon her role as a nurse, rather than abandoning it and adapting to a new quasi-role. If role mastery is to occur by gradual assimilation rather than by abrupt change, a nursing model is needed on which both preparation for and practice in the role can be based. The adaptation model provides the necessary framework to give direction to practitioner education; offers a relevant way of viewing the older adult in relation to his environment; and delineates guidelines for nurse practitioner action.