PubMed Health⌕ Search

Biomedical subjects

C A Phillips

Publications and source records attributed to C A Phillips.

At least 19 recordsLinked to original sources
PubMed1992

CD28-induced T cell activation. Evidence for a protein-tyrosine kinase signal transduction pathway.

CD28 is a 44-kDa homodimeric receptor expressed on the majority of T cells. Engagement of the CD28 receptor by soluble anti-CD28 mAb in conjunction with PMA causes the induction of lymphokine/cytokine production and proliferation in resting T cells via signal transduction pathways independent of the TCR. The precise nature of the biochemical events that occur after perturbation of the CD28 receptor remain unclear. We report evidence for the coupling of CD28 to a protein-tyrosine kinase pathway. Multivalent cross-linking of the CD28 receptor or stimulation by soluble CD28 mAb plus PMA, but not PMA or soluble CD28 mAb alone, reproducibly caused the rapid (within 2 min) tyrosine phosphorylation of a 100-kDa cellular substrate. In some experiments, additional cellular substrates of 110, 85, 74, 68, 56, 43, and 29 kDa were also observed. The tyrosine phosphorylation of these substrates was completely inhibited by 12 h pretreatment of T cells with herbimycin A, a selective inhibitor of src-family protein-tyrosine kinases. Pretreatment of T cells with herbimycin was without effect on CD28 surface expression but did inhibit CD28 mAb plus PMA-induced IL-2 mRNA levels, IL-2R(CD25) up-regulation, and cell proliferation. The inhibition of IL-2 mRNA levels was likely at the level of transcription, because herbimycin inhibited NF-AT, AP-1, and CD28RC but not NF-kappa B or OCT-1 binding activities to their respective IL-2 enhancer region sequences. Herbimycin did not inhibit PMA-dependent events including CD69 surface expression, NF-kappa B nuclear binding activity or the level of CD25 induced by PMA alone, supporting the notion that herbimycin is acting to inhibit a CD28 initiated or regulated protein-tyrosine kinase pathway(s).

Antigens, CD↗
PubMed1992

Antiquity of clonal salamander lineages revealed by mitochondrial DNA.

The existence of clonally reproducing vertebrates has often served as a foil in attempts to explain the near-ubiquity of sexual reproduction in eukaryotes, but the absence of recombination, with its attendant limitation of new genotypes to those produced through mutations, restricts the adaptive ability of clonal organisms. It has been argued, therefore, that clonal vertebrate taxa have short lifespans. Variation in mitochondrial DNA (mtDNA) within clonal populations is interpreted instead as reflecting multiple, although limited, independent hybridization events. On the basis of an analysis of an average of 373 nucleotide pairs, we report here that the mtDNA of clonal, hybrid, gynogenetic mole salamanders (Ambystoma, Ambystomatidae) differs by 5% or more from mtDNA of their closest possible sexual relatives (A. jeffersonianum, A. laterale and A. texanum). Assuming usual rates of mtDNA divergence, these lineages have persisted for about 5 million years, far longer than estimated for other clonal vertebrate populations. The low mtDNA variability in the clonal lineages suggests that they have undergone population reductions during the Pleistocene.

Ambystoma↗
PubMed1992

Velocity of mammalian skeletal muscle contraction as a function of fiber type, activation, initial length and temperature.

Multiple stepwise regression analyses techniques were applied to develop modifications of the Hill force-velocity equation. Specifically, predictive models of the Hill a coefficient, the Hill b coefficient, and isometric strength P0 were developed for the following set of variables: the fraction of slow-twitch fibers (X), the recruitment magnitude (A), the initial muscle length (L), and the muscle temperature (T). Results indicate that the Hill a and Hill b coefficients and isometric strength P0 can be predicted with a high degree of accuracy. The utility of the equation is that it would allow development of a computer program to control the velocity of contraction of muscles with differing fiber compositions and lengths such as are found in the leg.

Animals↗
PubMed1992

A noninvasive protocol for anterior temporal lobectomy.

We report the results of a protocol for choosing candidates for temporal lobectomy using a standard battery of objective tests without intracranial electrodes. We assigned each test a level of importance, and an algorithm was used to determine whether temporal lobectomy could be performed. Fifty-one patients (total pool, 103 patients) met protocol requirements and had an anterior temporal lobectomy with a mean follow-up of 39.4 months (range, 21 to 64 months), most remaining on anticonvulsant therapy. Eighty percent are seizure free, 12% have less than 3 seizures per year or only nocturnal seizures, and 8% have greater than 80% reduction in seizure frequency. One-third of patients who failed protocol criteria did not have temporal lobe seizures when studied with intracranial electrodes. We analyzed and modified the algorithm after comparing these patients with others who were poor candidates for temporal lobectomy. We conclude that this protocol is effective and recommend using such an objective algorithm.

Action Potentials↗
PubMed1992

Clinical liver disease in patients with rheumatoid arthritis taking methotrexate.

Between 1981 and 1989, 3 of 134 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) developed clinically significant hepatic dysfunction and showed histologic evidence of severe liver disease (fibrosis and cirrhosis). Factors identified in these patients that may have been linked to liver toxicity included diabetes, congestive heart failure and Felty's syndrome. In the patient group that received a post-MTX liver biopsy, pulmonary fibrosis and obesity were significantly associated with hepatic fibrosis/cirrhosis. Severe liver disease may occur in patients with RA treated with low dose MTX (less than 3%). Early liver biopsy is recommended in selected cases.

Aged↗
PubMed1991

Protection of monkeys against the lethal effects of male funnel-web spider (Atrax robustus) venom by immunization with a toxoid.

A stable toxoid was prepared from robustoxin (the lethal polypeptide neurotoxin in the venom of the male funnel-web spider, Atrax robustus) by polymerization with glutaraldehyde. This material was non-toxic in new-born mice. Administration of the toxoid to three Macaca fascicularis monkeys (50-80 micrograms/kg s.c. at 14-day intervals for 8-12 weeks) produced no toxic effects; anti-robustoxin antibodies were detected in serum samples by immunodiffusion tests within 13-27 days. In vivo evidence of successful protection with the toxoid was obtained by challenging the monkeys with male A. robustus venom (50 micrograms/kg i.v.) under anaesthesia with pentobarbitone (one monkey), or with ketamine, halothane and nitrous oxide, 1-26 weeks after the last injection of the toxoid. Only minor respiratory, cardiovascular and skeletal motor disturbances were produced, and all monkeys recovered fully and uneventfully. Challenge with the same dose of venom in non-immunized or robustoxin N-terminal decapeptide ovalbumin conjugate-treated monkeys resulted in typical lethal neurotoxic effects, culminating in severe hypotension or death from circulatory and respiratory failure within 280 min.

Amino Acid Sequence↗
PubMed1991

Walking while using a sensory tactile feedback system: potential use with a functional electrical stimulation orthosis.

A major limitation in the utilization of a functional electrical stimulation (FES) orthosis for routine, daily standing and walking of the spinal-cord-injured person is that visual monitoring is required to maintain balance and the walking pace. For standing and walking to be continuous and automatic with such an orthosis, a closed-loop sensory feedback system is proposed and evaluated; it provides vibrotactile feedback as a substitute to one's own visual sensation. Eight blindfolded experimental subjects were utilized as 'imitators' to interpret the footfalls of a second person (the pace setter). The experimental objective was to test the hypothesis that sufficient information could be transferred by way of the sensory (tactile) feedback system to the 'imitator' and to determine effectively foot position and anticipate the next step of the pacesetter. Quantitative analysis evaluated the effect of three different levels of training, under two different levels of cognitive load. The results disclosed a significant improvement in subject performance at the higher training levels compared with the 'no training' level (P = 0.01). Neither the cognitive load nor the interaction of training and cognitive load altered significantly the effect of training on subject performance. The experimental hypothesis is therefore satisfied that sufficient information was indeed transferred using the apparatus described. Such information (when utilized in conjunction with a thorough training programme) could be used in a practical sense by a paraplegic individual to interpret his own foot steps. Through continued use and training, it is likely that this information could become subconscious and automatic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Functional electrical stimulation and reciprocating gait orthosis for ambulation exercise in a tetraplegic patient: a case study.

The purpose of this paper is to report the cardiopulmonary stresses (as indicated by heart rate, blood pressure, oxygen consumption and task cost) for a tetraplegic individual when walking with electrical stimulation and a gait orthosis as opposed to walking with a gait orthosis alone. Functional electrical stimulation (FES), when interfaced with a reciprocating gait orthosis (RGO), resulted in walking exercise for a C-7 level tetraplegic subject, who was 8 years post-injury. Cardiopulmonary measurements were made and task costs calculated on this individual during progressive velocity walking with the FES-RGO and the orthosis alone (without FES). Results for the tetraplegic individual indicate that there were no significant changes in heart rate at the various walking velocities with respect to the two systems. However, systolic blood pressure was significantly reduced at the three highest walking velocities (1.2, 1.6 and 2.0 kph) when using the FES and orthosis system as compared to orthosis-alone walking (p less than .025, p less than .005 and p less than .025 respectively). Calculated oxygen consumption was significantly reduced and calculated task cost improved at the highest walking velocity (2.0 kph) when using the FES-RGO system as compared to using only the RGO (p less than .025). It is concluded that cardiopulmonary stresses are significantly less for this tetraplegic individual when ambulating at the higher velocities with electrical stimulation and a gait orthosis than when walking with a gait orthosis alone. This may result in improved endurance during each walking session and (consequently) an improved aerobic exercise effect. This might also allow some tetraplegics, who would be unable to walk with the RGO alone, to walk with electrical stimulation and the RGO.

Adult↗
PubMed1991

A systems approach to medically prescribed functional electrical stimulation. Ambulation after spinal cord injury.

A functional electrical stimulation (FES) system for ambulation of spinal cord injured patients has been described to consist of physician prescriptable, commercially available components. The system components are: electrical muscle stimulators, a reciprocating gait orthosis and the electrode delivery system. A systems approach to medically prescribed FES ambulation requires the interfacing of these basic components, each of which has the flexibility to adjust to the optimal configuration for each individual patient. The electrode delivery system is of central importance in interfacing the basic components. This report describes the electrode delivery system, a transcutaneous transducer garment, which allows a variety of electrode configurations and stimulation patterns. The system has been successfully employed on a C7 level tetraplegic patient and a T9 level paraplegic patient.

Adult↗
PubMed1990

Differential inhibition of T cell receptor signal transduction and early activation events by a selective inhibitor of protein-tyrosine kinase.

Engagement of the TCR (CD3-Ti) by Ag/MHC, CD3 mAb, or lectin mitogen stimulates the very early tyrosine phosphorylation of several cellular substrates including TCR-zeta. The T cell specific protein-tyrosine kinase (PTK), p56lck, has been implicated in the tyrosine phosphorylation of TCR-zeta. However, the significance of this event with regard to CD3-Ti signal transduction remains unclear. Herein, we have investigated the effect of the selective PTK inhibitor genistein (4',5,7-trihydroxyisoflavone) on cellular events associated with activation via CD3-Ti triggering. Genistein inhibited the T cell PTK, p56lck, in a dose-dependent fashion with an ID50 = 40 microM. Genistein also inhibited CD3 mAb or PHA-induced TCR-zeta chain phosphorylation in intact peripheral blood T cells. Genistein blocked the expression of IL-2 and IL-2R (CD25) in T cells stimulated with PHA/PMA or CD3 mAb/PMA, but did not inhibit the de novo expression of the CD69 early activation Ag, which is induced primarily by a PKC-dependent pathway. IL-2 and CD25 expression induced by calcium ionophore A23187 and PMA was largely refractory to inhibition by genistein, suggesting an effect of the drug on calcium-dependent pathways stimulated via CD3-Ti triggering. In this last regard, genistein partially inhibited the CD3 mAb-induced rise in [Ca2+]i but did not inhibit PHA- or CD3 mAb-induced phosphatidylinositol hydrolysis. Consequently, protein-tyrosine phosphorylation does not appear to be a prerequisite for CD3-Ti-mediated activation of phosphatidylinositol-specific phospholipase C activity and PIP2 hydrolysis. An alternative role for PTK in CD3-Ti signal transduction is suggested.

Antigens, CD↗
PubMed1990

Cardiac chemical constant. Part I: Derivation of the characteristic phenomenological equation.

A physiochemical parameter is derived and defined as the cardiac chemical equilibrium dissociation constant (KD). KD is based upon a phenomenological model in which the cardiac muscle chemical reaction kinetics describe the interconversion between long and short units (i.e. the individual sarcomere is fully extended or fully contracted). KD is defined as the ratio of the number of units in the long state to the number of units in the short state. The mathematical development proceeds through four stages: derivation of the governing differential equation during cardiac systole; simplification of the differential equation to describe the cardiac model; determination of the upper and lower limits and average value of Nt (the total number of units in a hypothetical mid-wall circumferential fibre): definition and calculation of the cardiac chemical constant (KD). KD is shown to describe a series of equilibrium points throughout cardiac systole. This requires that each mechanical equilibrium state (a series of static, steady-state intervals over time) is also associated with its own specific chemical equilibrium state.

Mathematics↗
PubMed1990

Cardiac chemical constant. Part II: Application to normal and abnormal left ventricular function.

A physiochemical parameter has been defined as KD, the cardiac chemical equilibrium dissociation constant, and represents the ratio of long units (extended sarcomeres) to short units (contracted sarcomeres) of a hypothetical mid-wall circumferential fibre. KD has been separately identified for three specific points in the cardiac cycle: end-diastole (KDED), mid-cycle of systole (KDMC) and end-systole (KDES). These three values of KD have been computed for 15 normal patients (N), 6 patients with compensated volume overload (CVO), 9 patients with decompensated volume overload (DVO), 3 patients with compensated pressure overload (CPO) and 6 patients with congestive cardiomyopathy (CC). The average for the N group was KDED = 2.47, KDMC = 0.67 and KDES = 0.24. The majority of the long-to-short unit interconversions were calculated to occur during the first half of systole. The phenomenological model does not predict any significant parameter changes between the CVO group and the N group. The ratio KDMC/KDED is significantly reduced (P less than 0.05) for the DVO group compared to the N group and indicates a greater extent of long-to-short unit interconversion during the first half of systole for the DVO group average (compared to the N group average). For the CPO group, KDED averages around 45% higher than the average normal (P less than 0.005) and KDES averages about 33% lower than the average of the N group (P less than 0.005). As a compensatory process in CPO, the myocardium is transferring a larger percentage of its total units (sarcomeres) to long units at end-diastole and interconverting a larger percentage of its long units to short units during systole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Electrical muscle stimulation in combination with a reciprocating gait orthosis for ambulation by paraplegics.

Commercially available electrical muscle stimulators (EMS) provide functional electrical stimulation and are interfaced with reciprocating gait orthosis (RGO). The system which has been developed is described here as an EMS-RGO. Advantages of the system include: medically prescriptable subsystems available from manufacturers, and commercially recommended subsystems for applications such as gait training. The system itself employs four EMS units worn on a belt. It is controlled by remote switches and is interfaced to electrodes placed over the quadriceps, hamstring and gluteal muscle groups of each leg. Two EMS units (for quadriceps stimulation) function primarily for stand-up and sit-down. Two other EMS units (for stimulation of the hip extensors) function primarily for ambulation. Each EMS unit is powered by a nine volt alkaline transistor battery which provides about 36 stand-uphs and sit-down's and approximately 3.1 km of walking before replacement is necessary. The system has been evaluated on a T-5 level paraplegic individual who sustained a motor complete lesion (Frankel Class B) of the spinal cord over seven years ago. It is emphasized that successful EMS-RGO walking exercise must be preceded by a physical conditioning programme of active physical therapy. New battery technology (such as lithium batteries) may improve the useful lifespan of the system, and new electrode technology (such as TTGs) may improve patient acceptance of the system.

Adult↗
PubMed1989

Muscular, respiratory and cardiovascular responses of quadriplegic persons to an F. E. S. bicycle ergometer conditioning program.

Seven quadriplegic subjects participated in F. E. S. bicycle ergometry, three times per week, over an eight week period. Left thigh girth measured at 20 cm above the knee increased from 44.4 cm pre-training to 46.5 cm post-training (p less than 0.05), and right thigh girth increased from 44.3 cm to 46.2 cm (p less than 0.05). Forced vital capacity increased from 3.23 liters (pre-training) to 3.42 liters (post-training) and was significant at the p less than 0.05 level. Forced inspiratory capacity increased for 3.30 liters, pre-training, to 3.42 liters, post-training (p less than 0.05). FEV1 (liters) increased from 2.77, pre-training to 3.07 post-training (p less than 0.05). All three respiratory parameters were 55%-60% of that predicted for normals. Significant changes were also found in resting cardiovascular data. Mean resting heart rate, pre-training, was 51.4 beats per minute compared to 54.5 beats per minute, post-training, (p less than 0.05). Resting cardiac output, pre-training was 4.14 L/min. compared to 4.47 L/min., post-training (p less than 0.05). Further analysis of the cardiovascular data showed that the increased heart rate post-training was associated with a decrease in the P-R interval from 0.186 sec., pre-training to 0.170 sec., post-training (p less than 0.05). Also, the increase in cardiac output, post-training was matched by an increase in the cardiac index from 2.21 L/min./M, pre-training, to 2.36 L/min./M, post-training (p less than 0.05). A statistically significant difference in the heart rate response to the cold pressor test was demonstrated (p less than 0.05) and a similar difference in the amount of heart rate response was seen during the tilt table test (p = 0.05).

Adolescent↗
PubMed1985

Evidence for a central component to the hypotensive action of ketanserin in the dog.

The mechanisms responsible for the hypotensive action of ketanserin are controversial. Vascular 5-HT2-receptor blockade, resulting in inhibition of serotonin-induced vasoconstriction and amplification of other vasoconstrictors, has been suggested by some investigators, but others have concluded that vascular alpha-adrenoceptor blockade is responsible. In our experiments using pentobarbitone-anaesthetized dogs, ketanserin (0.1-0.4 mg/kg i.v.) produced immediate and sustained falls in systemic arterial blood pressure and vascular resistance in the common carotid and femoral arterial circulations. Constrictor responses to noradrenaline in these circulations were unaffected by 0.1-0.4 mg/kg i.v. of ketanserin; alpha-adrenoceptor blockade was only produced by higher doses (1-4 mg/kg i.v.). Constrictor responses in the common carotid circulation to preganglionic cervical sympathetic nerve stimulation and to nicotine were not inhibited by 0.1-0.4 mg/kg of ketanserin. The systemic pressor responses to nicotine and common carotid artery occlusion, however, were reduced by these doses of ketanserin. These results suggest that alpha-adrenoceptor blockade is not responsible for the hypotensive action of 0.1-0.4 mg/kg of ketanserin, and that a centrally mediated inhibition of sympathetic nerve activity is involved.

Animals↗