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Biomedical subjects

J B Moore

Publications and source records attributed to J B Moore.

At least 19 recordsLinked to original sources
PubMed1992

Thiophene systems. 14. Synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxythieno[3,2-b]pyrans and related compounds as new potassium channel activators.

The synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxy-5,5-dimethylthieno[3,2-b]pyrans and related compounds are described. The compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats (SHR) and selected compounds were evaluated in vitro for increases in 86Rb efflux in rabbit isolated mesenteric arteries. The effects on activity in SHR of lactam ring size, the presence of heteroatoms in the lactam ring, the relative stereochemistry at C-6 and C-7, and the substituents on the thiophene ring are examined. The best racemic compound in this series is 32, trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-7-(2-oxopiperidin -1-yl)-5H- thieno[3,2-b]pyran, which is 10-fold more potent than cromakalim with an ED30 = 0.015 mg/kg in SHR. Compound 32 could be resolved and the antihypertensive activity determined to reside primarily in the (6S,7S)-(-)-enantiomer 41. Surprisingly, the elimination of water to give the enamides 50-52, thiophene isosteres of bimakalim, diminishes activity significantly.

Animals↗
PubMed1992

Steroid hormone synthesis by a vaccinia enzyme: a new type of virus virulence factor.

Vaccinia virus open reading frame (ORF) SalF7L has 31% amino acid identity to human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD). Here we show that SalF7L encodes an active 3 beta-HSD, by the conversion of pregnenolone to the steroid hormone progesterone. The gene is transcribed early during infection into a 1.4 kb mRNA from an initiation site 12 bp upstream of the ORF. An antiserum raised against bacterially expressed SalF7L immunoprecipitated a 38 kDa polypeptide from infected cells, but not from mock infected cells or from cells infected with a mutant virus from which the SalF7L ORF had been removed. Deletion of the gene had no effect on virus replication in CV-1 cells in culture, yet the deletion mutant was attenuated when intranasally inoculated into mice. This steroid hormone synthesizing enzyme is a novel type of virus virulence factor.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Heteroatom analogues of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones.

A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.

Animals↗
PubMed1992

Children's one-hand catching as a function of age, gender, and ball location.

A sizable body of literature exists on the product characteristics and developmental sequence for two-hand catching, but to date there is no description of the developmental characteristics of simple one-hand catching in young children. This study investigated the influence of age, gender, and ball location on children's one-hand catching. Boys and girls (N = 240) ranging in age from 5 to 12 years attempted to catch a total of 24 tennis balls, tossed from a 9-ft distance. Tosses were directed to four locations: (a) Waist, (b) Shoulder, (c) Above-the-Head, and (d) Out-to-the-Side. Descriptive data consisted of the percentage of successful catches at each ball location, and the hand-arm orientation selected by the child as a function of ball location. Results revealed that catching performance improved with age, boys caught more balls than girls, ball location influenced catching success, and, in general, the location of the toss constrained the child's selection of an appropriate hand-arm orientation. With the possible exception of the Shoulder location for girls, even very young children are sensitive to the perceptual aspects of the toss and respond with an appropriate orientation.

Age Factors↗
PubMed1991

Adaptive processing techniques based on hidden Markov models for characterizing very small channel currents buried in noise and deterministic interferences.

Techniques for characterizing very small single-channel currents buried in background noise are described and tested on simulated data to give confidence when applied to real data. Single channel currents are represented as a discrete-time, finite-state, homogeneous, Markov process, and the noise that obscures the signal is assumed to be white and Gaussian. The various signal model parameters, such as the Markov state levels and transition probabilities, are unknown. In addition to white Gaussian noise, the signal can be corrupted by deterministic interferences of known form but unknown parameters, such as the sinusoidal disturbance stemming from AC interference and a drift of the base line owing to a slow development of liquid-junction potentials. To characterize the signal buried in such stochastic and deterministic interferences, the problem is first formulated in the framework of a Hidden Markov Model and then the Expectation Maximization algorithm is applied to obtain the maximum likelihood estimates of the model parameters (state levels, transition probabilities), signals, and the parameters of the deterministic disturbances. Using fictitious channel currents embedded in the idealized noise, we first show that the signal processing technique is capable of characterizing the signal characteristics quite accurately even when the amplitude of currents is as small as 5-10 fA. The statistics of the signal estimated from the processing technique include the amplitude, mean open and closed duration, open-time and closed-time histograms, probability of dwell-time and the transition probability matrix. With a periodic interference composed, for example, of 50 Hz and 100 Hz components, or a linear drift of the baseline added to the segment containing channel currents and white noise, the parameters of the deterministic interference, such as the amplitude and phase of the sinusoidal wave, or the rate of linear drift, as well as all the relevant statistics of the signal, are accurately estimated with the algorithm we propose. Also, if the frequencies of the periodic interference are unknown, they can be accurately estimated. Finally, we provide a technique by which channel currents originating from the sum of two or more independent single channels are decomposed so that each process can be separately characterized. This process is also formulated as a Hidden Markov Model problem and solved by applying the Expectation Maximization algorithm. The scheme relies on the fact that the transition matrix of the summed Markov process can be construed as a tensor product of the transition matrices of individual processes.

Algorithms↗
PubMed1991

Bemoradan--a novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from canine heart tissue.

Canine cardiac muscle contains a type IV cyclic AMP (cAMP) phosphodiesterase (PDE) that is composed of two subtypes. One subtype is sensitive to rolipram inhibition (RSPDE), whereas the other is not inhibited significantly by rolipram (RIPDE). The RIPDE is inhibited by several cardiotonic agents operating by a PDE-inhibitory mechanism. Bemoradan [RWJ-22867; 7-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-2H-1,4-benzoxazin -3(4H)-one], a novel, potent positive inotropic agent, demonstrated biphasic inhibition of the fraction III enzyme from canine cardiac muscle. Inhibition by rolipram of the RSPDE converted the IC50 curves of bemoradan, indolidan, pimobendan, and imazodan to sigmoidal, monophasic curves. Lineweaver-Burk analysis yielded competitive inhibition KI values of 0.023, 0.09, 0.065 and 0.60 microM, respectively, for these compounds. The cardiotonic compounds, however, were not potent inhibitors of the Type I and Type II cAMP PDEs found in canine ventricular muscle. The order of potency for inhibiting the RIPDE cAMP PDE subtype was bemoradan greater than pimobendan greater than indolidan greater than imazodan. Bemoradan is, therefore, a potent inhibitor of the cardiac muscle cAMP PDE which could, in part, be responsible for its cardiotonic activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Proton NMR imaging of cerebral blood flow using H2(17)O.

Cerebral blood flow was quantitatively mapped by monitoring the cerebral washout of H2(17)O using rapid, single-shot proton NMR imaging. H2(17)O acts as a freely diffusible contrast agent for proton imaging via its scalar-coupled term, enhancing T2 relaxation. Measured values for CBF ranged from 29 to 106 ml/min/100 g over a range of arterial pCO2 between 23 and 81 Torr.

Animals↗
PubMed1990

Characterization of single channel currents using digital signal processing techniques based on Hidden Markov Models.

Techniques for extracting small, single channel ion currents from background noise are described and tested. It is assumed that single channel currents are generated by a first-order, finite-state, discrete-time, Markov process to which is added 'white' background noise from the recording apparatus (electrode, amplifiers, etc). Given the observations and the statistics of the background noise, the techniques described here yield a posteriori estimates of the most likely signal statistics, including the Markov model state transition probabilities, duration (open- and closed-time) probabilities, histograms, signal levels, and the most likely state sequence. Using variations of several algorithms previously developed for solving digital estimation problems, we have demonstrated that: (1) artificial, small, first-order, finite-state, Markov model signals embedded in simulated noise can be extracted with a high degree of accuracy, (2) processing can detect signals that do not conform to a first-order Markov model but the method is less accurate when the background noise is not white, and (3) the techniques can be used to extract from the baseline noise single channel currents in neuronal membranes. Some studies have been included to test the validity of assuming a first-order Markov model for biological signals. This method can be used to obtain directly from digitized data, channel characteristics such as amplitude distributions, transition matrices and open- and closed-time durations.

Animals↗
PubMed1990

Magnetic resonance imaging and neurobehavioral correlates in schizencephaly.

We studied three patients with schizencephaly and related the results of comprehensive neuropsychologic and speech/language assessments to the severity and location of the brain malformations as appreciated by magnetic resonance imaging. Level of general intellectual functioning related to the amount of brain tissue involved, and variations in specific neurobehavioral abilities reflected the location of the brain malformation and the prenatal onset of the disorder. The overall findings emphasize the importance of comprehensive neuropsychologic and speech/language studies for appreciating the impact of prenatal neural insult on the functional reorganization of the brain and subsequent neurobehavioral functioning.

Adolescent↗
PubMed1990

6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents.

A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely potent and selective inhibitor of canine PDE fraction III and a long-acting, potent, orally active inotropic vasodilator agent in various canine models. Additional benzoxazin-6-yl and -8-yl compounds were also prepared. Altering the pyridazinone substitution from the 6-position to the 7-position produced a 14-fold increase in the iv cardiotonic potency (ED50) from 77 to 5.4 micrograms/kg while substitution at the 8-position reduced potency. Methyl substitution at various sites in the molecule was also examined. Positive inotropic activity was maintained for between 8 and 24 h after a single oral dose (100 micrograms/kg) of bemoradan in dogs, thus making it one of the most potent and long-acting orally effective inotropes yet described. Bemoradan is currently under development as a cardiotonic agent for use in the management of congestive heart failure.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Conservative management of combined pancreatoduodenal injuries.

We have reviewed our recent 12-year experience in treating 62 patients with combined injuries to the pancreas and duodenum; 60 percent were the consequence of penetrating wounds and 40 percent due to blunt trauma. For analysis, grades I through V were assigned to reflect severity of injury. Grade I (16 percent) and II injuries (23 percent) were treated with simple repair and drainage. Grades III (19 percent) and IV (32 percent) were managed primarily by pyloric exclusion, whereas grade V injuries (10 percent) underwent pancreatoduodenectomy. Pancreatic and duodenal complications developed in 35 percent and 2 percent, respectively. The overall mortality was 19 percent; 83 percent died within the first 24 hours from exsanguination or severe head injury. Although no single procedure uniformly applies to the combined pancreatoduodenal trauma, active sump drainage of the pancreas, pyloric exclusion of the duodenum, and early nutritional support through needle catheter jejunostomy are the mainstay treatment principles.

Adult↗
PubMed1989

Emergency Department thoracotomy in children--a critical analysis.

Recent clinical reviews have helped to clarify the role of Emergency Department (E.D.) thoracotomy in critically injured adults. However, guidelines in the pediatric population remain ill defined. The purpose of this report is to examine the yield of E.D. thoracotomy in patients less than or equal to 18 years of age to allow for a more cost-effective application of this heroic measure. From an 11-year experience of 689 consecutive E.D. thoracotomies, 83 patients (12%) were less than or equal to 18 years old. Mechanism of injury was blunt trauma in 57%, gunshot wound in 30%, and stab wound in 13%. Mean age was 15 years and 71% were male. Survival by injury mechanism was 9% (1/11) for stab wound, 4% (1/25) for gunshot wound, and 2% (1/47) for blunt trauma. Sixty-nine patients presented to the E.D. without vital signs and only one, a 16-year-old with stab wounds to the chest and abdomen, survived. In contrast, two (14%) among 14 patients presenting with vital signs were salvaged. As in adults, outcome was largely determined by injury mechanism and physiologic status on E.D. presentation. Blunt trauma, the predominant mechanism of lethal injuries in children, had a dismal outcome, with only 2% salvage and no survivors when vital signs were absent. This study demonstrates a similar outcome for E.D. thoracotomy in children compared to adults, and supports a selective policy of liberal use in penetrating injury irrespective of physiologic status but limited in those arriving lifeless following blunt trauma.

Adolescent↗
PubMed1989

Development of an instrument to measure mothers' performance of self-care activities for children.

One who performs self-care activities for another is known as a dependent care agent, according to Orem. Attempts to study mothers' performance of self-care activities for children have been impeded by the lack of an instrument with which to measure dependent care agent performance. Findings based on a sample of 475 women indicate that the Dependent Care Agent (DCA) questionnaire developed in this study had a coefficient alpha of .91, with item-total correlations ranging from .27 to .63. Although Orem's expected dimensions of universal, developmental, and health deviation requisites were not represented in the factor analysis, individual requisites for self-care were clearly present.

Adult↗
PubMed1989

Introduction to magnetic resonance imaging.

Magnetic resonance imaging (MRI) has become an important diagnostic tool with a wide variety of clinical applications. This article provides a qualitative description of physical principles of MRI fundamental to an appreciation of the capabilities and limitations of this complex technology. The same physical principles are used to explain the appearance of the images and the ability of MRI to provide spectroscopic data. Contrast agents, types of MRI equipment, and the safety of MRI in carrying out patient population goals are discussed. This article provides background knowledge for two subsequent articles which cover clinical application of MRI in greater detail.

Humans↗
PubMed1989

Current indications for magnetic resonance imaging.

Magnetic resonance is a well-established imaging modality for CNS, but it's utility for visualizing the rest of the body has not been appreciated fully or exploited yet. The authors believe that MRI will become one of the primary imaging modalities for the body during the next several years. Current and future indications for magnetic resonance imaging of the body are discussed.

Adult↗