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Biomedical subjects

J A Davis

Publications and source records attributed to J A Davis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Use of vibrational angioplasty for the treatment of chronic total coronary occlusions: preliminary results.

The aim of the study was to investigate the feasibility and clinical safety of vibrational angioplasty in the treatment of chronic total coronary occlusions and evaluate the clinical and angiographic factors that are predictive of the procedural success and complications of the procedure. Seventy-eight patients with chronic total occlusions (>3 months) resistant to conventional techniques were treated by vibrational angioplasty using a variety of conventional guidewires. Lesions were successfully crossed in 67 (85.9%) cases and antegrade flow was achieved in 59 (75.5%). Major complications (myocardial infarction and tamponade) occurred in two (2.5%) patients, but no fatalities ensued. Angiographically detectable dissections were seen in 23 (29.5%) patients but only resulted in vessel compromise and reclosure in 5 cases. Multiple stepwise logistic regression analysis identified the duration (<6 months, P = 0.008) and the length of the occlusion (<15 mm, P = 0.03) as independent predictors of final success and the age of the patient (<55 years, P = 0.006) as the only independent predictor of procedural complications. Vibrational angioplasty is a safe technique useful in the treatment of chronic coronary occlusive disease. Patients in whom the procedure is likely to prove most successful may be easily identified by clinical and angiographic features (duration and length of occlusion).

Adult↗
PubMed1999

Cardio-respiratory responses to rowing ergometry and treadmill exercise soon after myocardial infarction.

PURPOSE: The aim of this study was to compare the cardio-respiratory differences between rowing ergometry and treadmill exercise in beta-blocked men participating in exercise rehabilitation soon after myocardial infarction (postMI). METHODS: Eleven males all receiving beta-blockade medication were measured for oxygen consumption (VO2), respiratory exchange ratio (RER), and rating of perceived exertion (RPE) at individualized submaximal exercise target heart rates (THR) during 6 min of exercise on each of a motorized treadmill and a rowing ergometer 2-6 wk (4.9 +/- 1.4) postMI. RESULTS: The mean THR of the group, predetermined from an exercise ECG stress test, was 107 +/- 16 beats x min(-1). No significant difference was found between rowing versus treadmill VO2 (19.4 +/- 3.2 vs 19.7 +/- 4.2 mL x kg(-1) x min(-1); P = 0.53) or RPE (12.6 +/- 1 vs 12.7 +/- 1; P = 0.72). RER was significantly greater (P = 0.02) during rowing (0.99 +/- 0.07) compared with treadmill exercise (0.94 +/- 0.07). CONCLUSION: Exercising at a specified submaximal THR during rowing versus treadmill exercise in beta-blocked men participating in very early cardiac rehabilitation represents the same VO2 and RPE. A significantly greater RER was, however, apparent during rowing compared with treadmill exercise; thus, agreement was shown with previous studies on healthy individuals where rowing ergometry was less metabolically efficient than treadmill exercise. The results suggest that establishing a THR from a standard treadmill stress test soon after MI is not only suitable for walking/treadmill exercise but also in setting exercise intensity for rowing ergometry.

Adrenergic beta-Antagonists↗
PubMed1999

Implanted functional electrical stimulation system for mobility in paraplegia: a follow-up case report.

A 16-channel functional electrical stimulation (FES) system has been implanted in a person with T10 paraplegia for over a year. The system consists of two eight-channel radio frequency controlled receiver-stimulators delivering stimuli through a network of 14 epimysial and two intramuscular electrodes. Using this system and a walker for support, the subject was able to stand up for 8 min and walk regularly for 20 m. The standing duration was limited by arm fatigue since upper extremities supported an average of 25% of body weight. This was due to suboptimal hip extension and some undesired recruitment of rectus femoris and sartorius with stimulation of quadriceps electrodes. The left quadriceps exhibited rapid fatigue that limited walking distance and duration. The metabolic energy requirements were well within the aerobic limits of the sedentary paraplegic population. At one-year follow-up evaluation all electrodes are functional except one intramuscular electrode. The implant caused no adverse physiological effects and the individual reported health benefits such as increased energy and overall fitness as a result of the FES system use. With further improvements in muscle response through innovative surgical techniques, the 16-channel implanted FES system can be a viable addition to exercise and mobility function in persons with paraplegia.

Adult↗
PubMed1999

Levels of bacterial community diversity in four arid soils compared by cultivation and 16S rRNA gene cloning.

Techniques based on amplification of 16S rRNA genes for comparing bacterial communities are now widely used in microbial ecology, but calibration of these techniques with traditional tools, such as cultivation, has been conspicuously absent. In this study, we compared levels of bacterial community diversity in two pinyon rhizosphere soil samples and two between-tree (interspace) soil samples by analyzing 179 cultivated bacterial isolates and 801 16S rRNA genes amplified from extracted soil DNA. Phylotypes were defined by performing a restriction fragment length polymorphism analysis of 16S rRNA gene sequences with the enzymes RsaI and BstUI. The average level of 16S rRNA gene sequence similarity of members of a phylotype was 86.6% based on an analysis of partial sequences. A total of 498 phylotypes were identified among the 16S ribosomal DNA (rDNA) clones, while 34 phylotypes occurred among the cultivated isolates. Analysis of sequences from a subset of the phylotypes showed that at least seven bacterial divisions were represented in the clone libraries, whereas the isolates represented only three. The phylotype richness, frequency distribution (evenness), and composition of the four culture collections and the four clone libraries were investigated by using a variety of diversity indices. Although cultivation and 16S rRNA cloning analyses gave contradictory descriptions of the relative phylotype richness for one of the four environments, the two methods identified qualitatively consistent relationships when levels of evenness were compared. The levels of phylotype similarity between communities were uniformly low (15 to 31%). Both methods consistently indicated that one environment was distinct from the other three. Our data illustrate that while 16S rDNA cloning and cultivation generally describe similar relationships between soil microbial communities, significant discrepancies can occur.

Bacteria↗
PubMed1999

Behavioral effects of ivermectin in mice.

BACKGROUND AND PURPOSE: Ivermectin is a common anthelmintic drug, widely used in laboratory rodents for treatment of pinworm and mite infestations. We evaluated the action of ivermectin on sensitive behavioral tasks in mice during treatment for mites within a barrier facility. METHODS: A total of 21 (5 males, 16 females) mice (129/SvEv) were used for measuring body weight, open field locomotor activity, and rotarod motor coordination. For acoustic startle and prepulse inhibition, 20 C57BL/6J and 29 AKR/J mice were studied. For the Morris water task, the same 20 C57BL/6J mice were studied. Ivermectin (0.08% sheep drench) was administered in the drinking water of the home cage for 8 weeks. Control groups received normal tap water in identical bottles. RESULTS: Ivermectin did not affect general health, body weight, motor coordination, swimming behavior, or spatial learning in several inbred strains of mice. However, it induced a small but significant effect on some sensitive behaviors. CONCLUSIONS: A cautious approach to initiating ivermectin treatment in mice should be used for sensitive behavioral experiments.

Acoustic Stimulation↗
PubMed1999

Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: dynamics of receptor inhibition in situ and antitumor effects in athymic mice.

Phosphorylation of tyrosine residues on the epidermal growth factor (EGF) receptor (EGFr) is an important early event in signal transduction, leading to cell replication for major human carcinomas. CP-358,774 is a potent and selective inhibitor of the EGFr tyrosine kinase and produces selective inhibition of EGF-mediated tumor cell mitogenesis. To assess the pharmacodynamic aspects of EGFr inhibition, we devised an ex vivo enzyme-linked immunosorbent assay for quantification of EGFr-specific tyrosine phosphorylation in human tumor tissue specimens obtained from xenografts growing s.c. in athymic mice. When coupled with pharmacokinetic analyses, this measurement can be used to describe the extent and duration of kinase inhibition in vivo. CP-358,774 is an effective, orally active inhibitor of EGFr-specific tyrosine phosphorylation (ED(50) = 10 mg/kg, single dose). It has a significant duration of action, producing, on average, a 70% reduction in EGFr-associated phosphotyrosine over a 24-h period after a single 100 mg/kg dose. Inhibition of EGFr phosphotyrosine in an ex vivo assay format effectively estimates the potency and degree of inhibition of EGFr-dependent human LICR-LON-HN5 head and neck carcinoma tumor growth. Substantial growth inhibition of human tumor xenografts was achieved with p.o. doses of the compound (ED(50) = 10 mg/kg q.d. for 20 days). Combination chemotherapy with cisplatin produced a significant response above that of cisplatin alone with no detectable effects on body weight or lethal toxicity. Taken together, these observations suggest that CP-358,774 may be useful for the treatment of EGFr-driven human carcinomas.

Animals↗
PubMed1998

The importance of the cortico-motoneuronal system for control of grasp.

Our recent work has revealed new evidence of the importance of direct cortico-motoneuronal (CM) connections for voluntary control of the hand. Most of these connections are derived from corticospinal neurons located in the M1 hand area, although there are some much smaller contributions from other secondary motor areas, such as the supplementary motor area (SMA). Intracellular recordings show that 75% of upper limb motoneurons in the chloralose-anaesthetized macaque monkey receive a monosynaptic projection from the corticospinal tract; evidence for non-monosynaptic, propriospinal excitatory influences from the corticospinal tract was conspicuously lacking in these anaesthetized preparations. Moreover, in the conscious monkey, hand and arm muscle motor unit responses to corticospinal tract input are dominated by single, brief peaks compatible with monosynaptic excitation. CM excitatory post-synaptic potentials, recorded from a comparable sample of hand and arm motoneurons in anaesthetized macaque and squirrel monkeys, were found to be larger and faster rising in the macaque, which is by far the more dexterous of the two species. CM cells facilitating a given muscle in the conscious macaque are distributed over a wide region of M1 cortex, and each contributes a particular pattern of discharge during a skilled task. In addition to their direct effects on target muscles there may be weaker but potentially important effects that derive from the synchronous binding of assemblies of output neurons. Synchronous oscillations between these neurons are particularly prevalent during steady grip, but disappear during digit movement.

Animals↗
PubMed1998

Determination of primary amino acid sequence and unique three-dimensional structure of WGH1, a monoclonal human IgM antibody with anti-PR3 specificity.

Transformed B cells making monoclonal IgM-lambda anti-PR3 antibody WGH1 from a patient with Wegener's granulomatosis were used to prepare mRNA and synthesize cDNA. PCR primers for human micro and lambda chains were then employed to amplify heavy- and light-chain V-regions followed by cloning into pCR2-1 vector and sequencing. Molecular modeling of VH regions employed knowledge-based homology modeling to obtain minimum energy conformation. The VH sequence was subgroup III with marked overall homology to VH1.9III. The VHCDR3 region of WGH1 was unique, consisting of 21 amino acid residues which included seven tyrosines as well as three negatively charged aspartic acid residues. The VL region was subgroup II with a negatively charged glutamic acid at position 100 in CDR3. Molecular modeling of VH revealed a major conformational difference in the shape of CDR3 compared with other antibodies for which three-dimensional structures have been determined. Monoclonal antibody WGH1 reacting with PR3 (a highly positively charged molecule) shows a unique reactive cassette within VHCDR3 with a number of negatively charged aspartic acid residues. WGH1 VHCDR3 contains a loop which shows a major projection not usually recorded in other previously studied antibody molecules.

Amino Acid Sequence↗
PubMed1998

An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos.

Mutations in presenilin 1 (PS1) cosegregate with approximately 25% of early onset familial Alzheimer's disease (FAD) pedigrees. A variety of in vitro and in vivo paradigms have established that one mechanism by which PS1 variants cause AD is by elevating the production of highly amyloidogenic Abeta1-42/43 peptides. PS1 is homologous to sel-12, a C. elegans protein that facilitates signaling mediated by the Notch/lin-12 family of receptors. Wild-type human PS1 complements an egg-laying defect in C. elegans lacking sel-12, while FAD-linked PS1 variants exhibit reduced rescue activity. These data suggested that mutant PS1 may cause disease as a result of reduction in PS1 function. To test the function of FAD-linked PS1 in mammals, we examined the ability of the A246E PS1 variant to complement the embryonic lethality and axial skeletal defects in mice lacking PS1. Finally, to examine the influence of reduced PS1 levels on Abeta production, we quantified Abeta1-42/43 peptide levels in PS1 heterozygous null mice (PS1[+/-] mice). We now report that both human wild-type and A246E PS1 efficiently rescue the phenotypes observed in PS1(-/-) embryos, findings consistent with the view that FAD-linked PS1 mutants retain sufficient normal function during mammalian embryonic development. Moreover, the levels of Abeta1-42/43 and Abeta1-40 peptides between PS1(+/-) and control mice are indistinguishable. Collectively, these data lead us to conclude that mutant PS1 causes AD not by loss of normal PS1 function but by influencing amyloid precursor protein (APP) processing in a manner that elevates Abeta1-42/43 production.

Alzheimer Disease↗