Biomedical subjects

D McPherson

Publications and source records attributed to D McPherson.

At least 19 recordsLinked to original sources

PubMed2001

Adjunctive therapies in the cath lab. Successful thrombolysis using the combination of tissue plasminogen activator and abciximab in an adult with Kawasaki's disease.

Kawasaki's disease is an acute systemic vasculitic syndrome that primarily affects children. Coronary aneurysms are common vasculitic sequelae of Kawasaki's disease. Intracoronary thrombosis and embolization are potential consequences of coronary aneurysms. We describe our experience of successful thrombolysis using the combination of reduced-dose intravenous tissue plasminogen activator and abciximab as described in the Thrombolysis in Myocardial Infarction 14 trial (TIMI 14) to treat a patient found to have intracoronary thrombus at the site of aneurysm formation due to Kawasaki's disease.

Abciximab↗

PubMed1999

Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M(1 )and M(2) muscarinic acetylcholine receptors in Alzheimer's disease.

Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z-IQNP) has high affinity to the M(1 )and M(2) muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[(123)I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[(123)I]IQNP binding in all these regions. The percentage of unchanged Z-[(123)I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[(123)I]IQNP showed higher uptake in M(2)-rich regions, compared with previously obtained results with E-[(123)I]IQNP. In conclusion, the radioactivity distribution from Z-[(123)I]IQNP in monkey brain indicates that Z-[(123)I]IQNP binds to the M(1)- and M(2)-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.

Alzheimer Disease↗

PubMed1999

Professional advertising and your optometric practice.

As advertising by health care professionals becomes more common, it is possible to gain the benefits of well-designed advertising without sacrificing professionalism. This author explains how, with a special emphasis on Yellow Pages advertising.

Advertising↗

PubMed1998

Engineering protein-based machines to emulate key steps of metabolism (biological energy conversion)

Metabolism is the conversion of available energy sources to those energy forms required for sustaining and propagating living organisms; this is simply biological energy conversion. Proteins are the machines of metabolism; they are the engines of motility and the other machines that interconvert energy forms not involving motion. Accordingly, metabolic engineering becomes the use of natural protein-based machines for the good of society. In addition, metabolic engineering can utilize the principles, whereby proteins function, to design new protein-based machines to fulfill roles for society that proteins have never been called upon throughout evolution to fulfill. This article presents arguments for a universal mechanism whereby proteins perform their diverse energy conversions; it begins with background information, and then asserts a set of five axioms for protein folding, assembly, and function and for protein engineering. The key process is the hydrophobic folding and assembly transition exhibited by properly balanced amphiphilic protein sequences. The fundamental molecular process is the competition for hydration between hydrophobic and polar, e.g., charged, residues. This competition determines Tt, the onset temperature for the hydrophobic folding and assembly transition, Nhh, the numbers of waters of hydrophobic hydration, and the pKa of ionizable functions. Reported acid-base titrations and pH dependence of microwave dielectric relaxation data simultaneously demonstrate the interdependence of Tt, Nhh and the pKa using a series of microbially prepared protein-based poly(30mers) with one glutamic acid residue per 30mer and with an increasing number of more hydrophobic phenylalanine residues replacing valine residues. Also, reduction of nicotinamides and flavins is shown to lower Tt, i.e., to increase hydrophobicity. Furthermore, the argument is presented, and related to an extended Henderson-Hasselbalch equation, wherein reduction of nicotinamides represents an increase in hydrophobicity and resulting hydrophobic-induced pKa shifts become the basis for understanding a primary energy conversion (proton transport) process of mitochondria. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

PubMed1997

Characterization of recombinant yeast dolichyl mannosyl phosphate synthase and site-directed mutagenesis of its cysteine residues.

Dolichyl mannosyl phosphate synthase is associated with membranes of the rough endoplasmic reticulum and catalyzes mannosyl transfer from GDP-mannose to the hydrophobic long-chain acceptor dolichyl-phosphate. The gene for the yeast enzyme encodes a protein with a molecular mass of 30.36 kDa containing three cysteine residues, at positions 93, 172 and 259 [Orlean, P., Albright, C. & Robbins, P. W. (1988) J. Biol. Chem. 263, 17499-17507]. Inhibition of the synthase by thiol-specific reagents, including N-ethylmaleimide, p-hydroxymercuribenzoate, 5,5'-dithiobis(2-nitrobenzoic acid) (Nbs2), and lucifer yellow iodoacetamide (LYI), suggests that sulfhydryl groups might play a role in the catalytic mechanism of the enzyme. Titration of the synthase with Nbs2 or LYI indicated that 1 mol sulfhydryl/mol protein was accessible to these reagents, and that saturation of this site completely inhibited enzyme activity. To ascertain the reactive group and its possible function in enzyme catalysis, each of the cysteine residues was replaced individually by site-directed mutagenesis. The mutant enzymes had specific activities comparable to that of the wild-type enzyme, demonstrating that none of the cysteine residues were essential for catalytic activity. All of the mutant proteins except those containing a substitution at Cys93 were inhibited by thiol-blocking reagents, indicating that Cys93 might be physically located near the catalytic site of the enzyme. GDP-mannose, dolichyl phosphate and substrate analogs were found to protect against Nbs2 inactivation, further suggesting that Cys93 was physically near, or within, the substrate-binding site of the enzyme.

Binding Sites↗

PubMed1996

Comparison of Perillus bioculatus and Podisus maculiventris (Hemiptera:Pentatomidae) as potential control agents of the Colorado potato beetle (Coleoptera:Chrysomelidae).

In laboratory and microplot consumption tests, spined soldier bug, Podisus maculiventris (Say), ate at least as many Colorado potato beetle, Leptinotarsa decemlineata (Say), eggs and larvae as did the twospotted stink bug, Perillus bioculatus (F.). P. maculiventris also remained in field microplots infected with Colorado potato beetle egg masses for slightly longer than did P. bioculatus. The 2 predators were equally effective at consuming egg masses, reducing densities of beetle larvae, and preventing potato defoliation in small field plots. These results contrast with previous trials, in which P. bioculatus had been more effective. In laboratory trials, larger P. maculiventris nymphs selected larger prey larvae, whereas P. bioculatus nymphs did not discriminate by size of prey; thus, the relative effectiveness of the 2 predators may depend on the life stages of the prey that are present at the time of predator release.

Animals↗

PubMed1995

An aspartic acid at amino acid 108 is required to rescue infectious virus after transfection of a poliovirus cDNA containing a CGDD but not SGDD amino acid motif in 3Dpol.

The poliovirus RNA-dependent RNA polymerase (3Dpol) contains a region of homology centered around the amino acid motif YGDD (amino acids 326 to 329), which has been postulated to be involved in the catalytic activity of the enzyme. Previous studies from this laboratory have used oligonucleotide site-directed mutagenesis to substitute the tyrosine amino acid at this motif with other amino acids (S. A. Jablonski and C. D. Morrow, J. Virol. 67:373-381, 1993). The viruses recovered with 3Dpol genes with a methionine mutation also contained a second mutation at amino acid 108 resulting in a glutamic acid-to-aspartic acid change (3D-E-108 to 3D-D-108) in the poliovirus RNA polymerase. On the basis of these results, we suggested that the amino acid at position 108 might interact with the YGDD region of the poliovirus polymerase. To further investigate this possibility, we have constructed a series of constructs in which the poliovirus RNA polymerases contained a mutation at amino acid 108 (3D-E-108 to 3D-D-108) as well as a mutation in which the tyrosine amino acid (3D-Y-326) was substituted with cysteine (3D-C-326) or serine (3D-S-326). The mutant 3Dpol polymerases were expressed in Escherichia coli, and in vitro enzyme activity was analyzed. Enzymes containing the 3D-D-108 mutation with the wild-type amino acid (3D-Y-326) demonstrated in vitro enzyme activity similar to that of the wild-type enzyme containing 3D-E-108. In contrast, enzymes with the 3D-C-326 or 3D-S-326 mutation had less in vitro activity than the wild type. The inclusion of the second mutation at amino acid 3D-D-108 did not significantly affect the in vitro activity of the polymerases containing 3D-C-326 or 3D-S-326 mutation. Transfections of poliovirus cDNAs containing the substitution at amino acid 326 with or without the second mutation at amino acid 108 were performed. Consistent with previous findings, we found that transfection of poliovirus cDNAs containing the 3D-C-326 or 3D-S-326 mutation in 3Dpol did not result in the production of virus. Surprisingly, transfection of the poliovirus cDNAs containing the 3D-D-108/C-326 double mutation, but not the 3D-D-108/S-326 mutation, resulted in the production of virus. The virus obtained from transfection of polio-virus cDNAs containing 3D-D-108/C-326 mutation replicated with kinetics similar to that of the wild-type virus. RNA sequence analysis of the region of the 3Dpol containing the 3D-C-326 mutation revealed that the codon for cysteine (UGC) reverted to the codon for tyrosine (UAC). The results of these studies establish that under the appropriate conditions, poliovirus has the capacity to revert mutations within the YGDD amino acid motif of the poliovirus 3Dpol gene and further strengthen the idea that interaction between amino acid 108 and the YGDD region of 3Dpol is required for viral replication.

Amino Acid Sequence↗

PubMed1994

Combined retrograde labeling and calcium imaging in spinal cord and brainstem neurons of the lamprey.

Neurons in the brainstem and spinal cord of the lamprey were retrogradely labeled with Calcium Green-dextran, an indicator dye that increases its fluorescence when intracellular calcium levels increase. Optical signals could be recorded from these labeled neurons during spinal cord stimulation, nerve stimulation, or spontaneous activity, up to 4 days after dye application and for distances of 5-14 mm away from the application site. Optical signals were enhanced by 4-AP, a potassium channel blocker, and blocked by cadmium, a calcium channel blocker. Taken together, the results suggest that the optical signals recorded from labeled neurons were due to calcium influx during electrical activity. Thus, retrograde labeling with calcium indicator dyes may provide a general purpose method for simultaneously monitoring the activity-related changes of intracellular calcium in anatomically identified groups of neurons in the lamprey nervous system.

4-Aminopyridine↗

PubMed1992

Postoperative posterior spinal wound infections.

The incidence of postoperative spinal infections increases with the complexity of the procedure. Diskectomy is associated with less than a 1% risk of infection; spinal fusion without instrumentation is associated with a 1%-5% risk; and fusion with instrumentation may be associated with a risk of 6% or more. Twenty-two postoperative posterior spinal infections that occurred during a three-year period were reviewed for this report. Staphylococcus aureus was the most frequent organism cultured (more than 50% of the cases). Other recurring organisms were Staphylococcus epidermis, Peptococcus, Enterobacter cloacae, and Bacteroides. Many patients had multiple organisms. Risk factors appeared to include advanced age, prolonged hospital bed rest, obesity, diabetes, immunosuppression, and infection at remote sites. Operative factors included prolonged surgery (greater than five hours), high volume of personnel moving through the operating room, and instrumentation. Postoperative contamination may occur and may be related to prolonged postoperative bed rest, skin maceration (thoracolumbosacral orthoses), and drainage tubes exiting distally from lumbar wounds (toward the rectum). Effective treatment includes early diagnosis, surgical debridement and irrigation, and parenteral antibiotics. Superficial infections were treated successfully with wound closure over outflow tubes, and deep infections with inflow-outflow systems. Maintaining the instrumentation in place was possible in most cases. Parenteral antibiotics were maintained for six weeks in every case.

Anti-Bacterial Agents↗

PubMed1992

The role of bronchoalveolar lavage in patients considered for open lung biopsy.

In summary, BAL should be considered as a diagnostic alternative in many patients for whom open lung biopsy is considered. In the proper clinical setting, several disorders may be adequately confirmed or diagnosed by BAL, with or without transbronchial biopsy, avoiding the morbidity and mortality associated with open lung biopsy. Again in the immune-compromised host with diffuse pulmonary infiltrates, BAL is often the initial procedure of choice. In the future BAL will likely gain a more prominent role in the staging of interstitial and occupational lung diseases, as larger prospective studies are concluded.

Biopsy↗

PubMed1991

Functional and morphological evidence for the existence of neurites from abdominal ganglion bag cell neurons in the head-ring ganglia of Aplysia.

Three lines of evidence are presented indicating that axons of the Aplysia neuroendocrine bag cells extend into the head-ring ganglia of the CNS. When the abdominal ganglion was bisected longitudinally, separating the two bag cell clusters, an afterdischarge induced in one cluster generated an afterdischarge in the other via activity through the head-ring ganglia to which each half abdominal ganglion was attached by connective nerves. This suggests that some axons of bag cells in each cluster communicate through the head-ring ganglia. Retrograde labelling of bag cells occurred when rhodamine-conjugated latex microspheres were injected into the cerebral or either pleural ganglion, a direct demonstration that bag cell axons extend into these ganglia. Finally, cell LP1 in the left pleural ganglion was inhibited during a bag cell afterdischarge, an action mimicked by application of alpha-bag cell peptide (alpha BCP). Since alpha BCP can act only close to its site of release due to susceptibility to peptidase activity, it is likely that LP1 inhibition is dependent on the local release of alpha BCP from bag cell neurites in the pleural ganglion. These results open new possibilities for how bag cell afterdischarges may be initiated and broaden the distribution of their effects.

Abdomen↗

PubMed1991

Absence of both auditory evoked potentials and auditory percepts dependent on timing cues.

An 11-yr-old girl had an absence of sensory components of auditory evoked potentials (brainstem, middle and long-latency) to click and tone burst stimuli that she could clearly hear. Psychoacoustic tests revealed a marked impairment of those auditory perceptions dependent on temporal cues, that is, lateralization of binaural clicks, change of binaural masked threshold with changes in signal phase, binaural beats, detection of paired monaural clicks, monaural detection of a silent gap in a sound, and monaural threshold elevation for short duration tones. In contrast, auditory functions reflecting intensity or frequency discriminations (difference limens) were only minimally impaired. Pure tone audiometry showed a moderate (50 dB) bilateral hearing loss with a disproportionate severe loss of word intelligibility. Those auditory evoked potentials that were preserved included (1) cochlear microphonics reflecting hair cell activity; (2) cortical sustained potentials reflecting processing of slowly changing signals; and (3) long-latency cognitive components (P300, processing negativity) reflecting endogenous auditory cognitive processes. Both the evoked potential and perceptual deficits are attributed to changes in temporal encoding of acoustic signals perhaps occurring at the synapse between hair cell and eighth nerve dendrites. The results from this patient are discussed in relation to previously published cases with absent auditory evoked potentials and preserved hearing.

Acoustic Stimulation↗

PubMed1990

Long-term neurophysiologic outcome after neonatal extracorporeal membrane oxygenation.

We examined clinical and neurophysiologic measures in 10 children 4 to 9 years after neonatal extracorporeal membrane oxygenation. Electroencephalograms did not correlate with clinical or other neurophysiologic measures of interhemispheric asymmetry. By ultrasound imaging, the right internal carotid artery velocity was approximately 62% of that on the left, and right internal carotid flow was reduced by 74% (p less than or equal to 0.01), whereas an age-matched control group showed no differences. A decrease in the amplitude of the long-latency auditory and somatosensory evoked potentials was noted over the right hemisphere after left-sided stimulation compared with the left hemispheric potentials after right-sided stimulation (p less than or equal to 0.005). No significant differences in hemispheric symmetry were noted in the amplitudes for wave V of the auditory brain-stem response or in the P30 component of the middle-latency auditory evoked potentials. Likewise, latency measures of the evoked potentials were symmetric. We conclude that (1) neonatal extracorporeal membrane oxygenation is associated with long-lasting decreased right internal carotid blood flow with compensatory increased flow through the left carotid system and (2) there is a consistent reduction in the amplitude of right hemispheric long-latency evoked potentials. These latter findings may reflect redirected cerebral blood flow patterns after extracorporeal membrane oxygenation.

Blood Flow Velocity↗

PubMed1990

Functional chiral asymmetry in descending thoracic aorta.

To determine whether rotational blood flow or chiral asymmetry exists in the human descending thoracic aorta, we established the ability of color Doppler ultrasound to detect rotational flow in a tornado tube model of a vortex descending fluid column. In a model of the human aortic arch with a pulse duplicator, color Doppler was then used to demonstrate that rotational flow occurs first in the transverse arch and then in the proximal descending thoracic aorta. With the use of color Doppler esophageal echocardiography, 53 patients (age range, 25-78 years; mean age, 56.4 years) were prospectively examined for rotational flow in the descending thoracic aorta. At 10 cm superior to retro-left ventricular position, 22 of 38 patients (58%) revealed rotational flow with obvious diastolic counterclockwise rotation but less obvious systolic clockwise rotation. At 5 cm superior to retro-left ventricular position, 29 of 46 patients (63%) revealed rotational flow with a tendency toward systolic clockwise and diastolic counterclockwise rotation. At the retro-left ventricular position, 47 of 53 patients (89%) revealed rotational flow, usually of a clockwise direction, occurring in systole. Our data suggest that aortic flow is not purely pulsatile and axial but has a rotational component. Rotational flow begins in the aortic arch and is carried through to the descending thoracic aorta, where flow is chirally asymmetric with systolic clockwise and diastolic counterclockwise components. These data demonstrate an aortic rotational flow component that may have physiological implications for organ perfusion.

Adult↗

PubMed1989

5-Fluorouracil-induced angina.

5-Fluorouracil-induced cardiac ischemia is rare and poorly understood. We present the second known case of catheterization data and provide new information regarding possible mechanisms.

Aged↗

PubMed1987

Electrophysiologic studies in selective dorsal rhizotomy for spasticity in children with cerebral palsy.

A group of 20 children with spastic cerebral palsy underwent selective dorsal rhizotomy for alleviation of spasticity. Pre- and postoperatively, cortical somatosensory evoked responses (cSSEP), H reflex and F wave studies were done. Clinically there was dramatic reduction of tone without noticeable sensory loss. The electrophysiologic studies showed several findings: (1) many children have abnormal cSSEP preoperatively; (2) surgery seldom leads to a loss of cSSEP; (3) in many patients, there is a noteworthy improvement in the cSSEP wave form; (4) some children have electrophysiologic evidence of spinal cord dysfunction preoperatively and (5) Hmax/Mmax ratio decreases after surgery confirming decrease in tone.

Cerebral Palsy↗

PubMed1987

Serial PET studies of human cerebral malignancy with [1-11C]putrescine and [1-11C]2-deoxy-D-glucose.

Serial PET measurements of [1-11C]putrescine ([11C]PUT) uptake and glucose metabolic rate (GMR) using [1-11C]2-deoxy-D-glucose ([11C]2DG) were made on eight human subjects with a radiological and, in most cases, pathological diagnosis of primary or metastatic brain tumor. Blood-to-brain influx constants (Ki) were calculated for [11C]PUT. Tumor uptake of 11C after [11C]PUT injection was unidirectional peaking at 15 min. The mean +/- s.d. Kis for [11C]PUT for tumor and normal brain tissue were 0.78 +/- 0.045 and 0.024 +/- 0.007 ml cc-1 min-1, respectively (average of ratio, 3.11) whereas the ratio of GMR for tumor and normal brain tissue was 1.2 +/- 0.5. The mean Ki for four active, high grade astrocytomas was 0.098 +/- 0.030 in contrast to 0.027 +/- 0.008 ml cc-1 min-1 for two patients with low grade astrocytoma. Active high grade astrocytomas also showed marked CT contrast enhancement and regional glucose hypermetabolism. In one subject with brain metastases, both [11C]PUT and GMR correlated with a declining clinical picture in repeated studies over a 4-mo period. PET studies with [11C]PUT provide a better signal:noise ratio than GMR measurements, are useful for locating small glycolytically hypometabolic tumors and, when used in longitudinal studies in a single subject, appear to provide an index of degree of malignancy.

Adult↗

PubMed1985

Automated impedance-based energy adjustment for defibrillation: experimental studies.

In defibrillation, current flow depends on the energy selected and the transthoracic impedance. If transthoracic impedance is high, current flow may be inadequate to defibrillate. We developed a method by which high transthoracic impedance is automatically compensated for by an increase in operator-selected energy when impedance is high. Transthoracic impedance was predicted in advance of the first shock by passing a low-level current between the defibrillator electrodes during the defibrillator charge cycle; a microprocessor monitored current flow and determined impedance. In 28 mongrel dogs we manipulated transthoracic impedance by placing glycerin-soaked gauze pads between the paddle electrodes and the chest. If the predicted impedance exceeded a preset value, the delivered energy was automatically increased by 40% or 100%. Using this impedance-based energy adjustment technique, we found significant improvements in current flow and success rate of shocks when energy was automatically increased to compensate for high transthoracic impedance. The use of transthoracic impedance as a basis for energy adjustment appears a promising technique to minimize the hazards of high electrical energy; it allows low-energy shocks in most patients while avoiding inappropriate low energies in patients with high impedance. Clinical trials are justified.

Animals↗