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Biomedical subjects

J S Davis

Publications and source records attributed to J S Davis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prostaglandin F2alpha stimulates the Raf/MEK1/mitogen-activated protein kinase signaling cascade in bovine luteal cells.

Upon binding to its G protein-coupled transmembrane receptors, the actions of PGF2alpha on the corpus luteum are initiated by the phospholipase C/diacylglycerol-inositol 1,4,5-trisphosphate (InsP3)/Ca2+-protein kinase C (PKC) pathway. However, little is known about the downstream intracellular signaling events that can lead to transcriptional activation in response to PGF2alpha. The present study was conducted to examine the involvement of the mitogen-activated protein kinase (MAPK) signaling cascade in the corpus luteum. Three isoforms of the Raf family of oncoprotein kinases (A-Raf, B-Raf, and Raf-1 or c-Raf) were detected in bovine luteal cells. Raf-1 and B-Raf, but not A-Raf, were activated by PGF2alpha (1 microM) and the pharmacological PKC activator phorbol myristate acetate (PMA, 20 nM). Kinetic analysis revealed that PGF2alpha rapidly and transiently activated Raf-1. In vitro protein kinase assays demonstrated that activation of Raf-1 and B-Raf resulted in the phosphorylation and activation of MAPK kinase (MEK1), which subsequently phosphorylated p42mapk. As determined by hyperphosphorylation, tyrosine phosphorylation, and enzymatic activity, p42mapk and p44mapk were rapidly and transiently activated by both PGF2alpha (1 microM) and PMA (20 nM). Additionally, both PGF2alpha (1 microM) and PMA (20 nM) stimulated phosphorylation of Raf-1, MEK1, and p42mapk in 32P-labeled cells. Our data demonstrate that PGF2alpha activates the Raf/MEK1/p42/44mapk signaling cascade in bovine luteal cells and that the actions of PGF2alpha are mimicked by the PKC activator PMA. Activation of the Raf/MEK1/MAPK signaling cascade by PGF2alpha in luteal cells provides a mechanism to transduce signals initiated by PGF2alpha receptors on the cell surface into the nucleus. Activation of the Raf/MEK1/MAPK signaling cascade may be associated with transcriptional activation of luteal genes possessing activator protein-1-binding sites.

Animals↗
PubMed1998

Force generation simplified. Insights from laser temperature-jump experiments on contracting muscle fibers.

Raising the temperature of a maximally Ca(2+)-activated muscle fiber causes a sigmoidal increase in tension. The kinetics that govern this process can be explored by step-heating the fiber a few degrees with a laser temperature-jump. A biexponential increase in tension results; a third exponential phase that opposes this biphasic rise in tension is only observed when phosphate, a reaction product normally at low concentration, is added to the fiber. This chapter explains how the temperature dependencies of isometric tension and the temperature jump kinetics interrelate, and how these insights have modified and simplified our understanding of current mechanisms of force generation. The fast kinetic phase of the tension rise appears associated with single-step force generation or a power stroke, a process largely isolated from adjacent steps in the crossbridge cycle. The amplitude of the slow phase of the tension rise exhibits a remarkable approximately 1:1 ratio to the amplitude of the fast, tension generating phase above 10 degrees C. The similarity of these two amplitudes, that combine to give the complete rise in isometric tension with temperature, appear to fit a model in which one of a pair of myosin heads generates force while the second head is poised to function after the power stroke of the first has occurred. The phase with the negative amplitude seen with added phosphate points to a mechanism in which phosphate release is indirectly linked to the tension generation by forward flow through the crossbridge cycle to tension generation.

Animals↗
PubMed1997

Meeting the frustrations of chronic fatigue syndrome.

Patients face long-term disability, a variable prognosis, and too often, skeptical or misinformed doctors. Physicians lack laboratory markers or definitive treatment. Nevertheless, the diagnosis can be made with confidence by applying established diagnostic criteria- and selected laboratory studies to exclude other disorders-while symptomatic medication can provide support until recovery begins.

Adult↗
PubMed1997

Secondary intraocular lens implantation after cataract surgery in children.

PURPOSE: To report results of secondary intraocular lens implantation after cataract surgery in children. METHODS: We reviewed clinical records for a 5-year period of patients who had cataract surgery in childhood and received a secondary intraocular lens implant. We studied indications for secondary intraocular lens placement; surgical procedures for intraocular lens implantation; preoperative and postoperative visual acuity, refractive error, and binocular status; and complications of the procedure. RESULTS: A secondary intraocular lens was placed in 28 eyes of 25 patients who had cataract surgery in childhood. In 20 eyes, the lenses were placed in the ciliary sulcus. The other eight eyes had insufficient capsular support for an intraocular lens; in two, the intraocular lens was placed in the anterior chamber and, in six, in the posterior chamber with suture fixation to the sclera. Twenty of 28 eyes (71%) had measurable improvement in visual acuity; only one eye had a decrease in visual acuity of 2 lines. Fifteen patients (54%) had a final refraction within 1.50 diopters of the fellow eye; 21 (75%) were within 3.00 diopters. During follow-up, two eyes developed glaucoma. One had transient pressure elevation; one required two filtration procedures. Three patients required Nd:YAG capsulotomy. Six patients demonstrated Worth fusion at distance and near; three demonstrated 200 seconds of arc or better stereo visual acuity. CONCLUSION: Secondary placement of an intraocular lens in the posterior chamber appears to be a safe, effective alternative for correction of aphakia in the contact lens- or spectacles-intolerant child or young adult.

Adolescent↗
PubMed1996

Mechanisms of hormone and growth factor action in the bovine corpus luteum.

The binding of hormones and growth factors to their cell surface receptors leads to an orderly cascade of events leading to activation of cytoplasmic effector molecules. The mechanism of action of luteinizing hormone involves the stimulation of multiple signal transduction effector systems including adenylyl cyclase and inositol phospholipid-specific phospholipase C (PLC). This results in the formation of second messengers that activate cAMP-dependent, Ca(2+)-dependent and lipid-dependent protein kinases. Prostaglandin F(2alpha) activates PLC which increases intracellular calcium and activates protein kinase C. This results in the activation of a series of protein kinases in the mitogen-activated protein (MAP) kinase cascade, leading to the activation of nuclear transcription factors c-fos and c-jun. Hormone responsive effector systems, therefore, operate by activating families of protein kinases which regulate cell metabolism, secretion, and gene transcription. Growth factors activate specific receptor protein tyrosine kinases which recruit additional signaling molecules (phospholipase Cgamma, phosphatidylinositol 3-kinase, Shc, Grb2, etc.) initiating a cascade of events mediated via MAP kinases. The signaling pathways activated by hormones interact or cross talk with the signaling pathways activated by growth factors. The diversity of cellular signaling mechanisms elicited by hormones and the potential for interactions with signals generated by growth factor receptor tyrosine kinases, may allow fine tuning of cellular responses during the life span of the corpus luteum.

Journal Article↗
PubMed1996

X-ray diffraction studies on thermally induced tension generation in rigor muscle.

Muscle fibres in the rigor state and free of nucleotide contract if heated above their physiological working temperature. Kinetic studies on the mechanism of this process, termed rigor contraction, indicate that it has a number of features in common with the contraction of maximally Ca2+ activated fibres. De novo tension generation appears to be associated with a single, tension sensitive, endothermic step in both systems. Rigor contraction differs in that steps associated with crossbridge attachment and detachment are absent. We investigated structural changes associated with rigor contraction using X-ray diffraction. Overall changes in the low angle X-ray diffraction pattern were surveyed using a two-dimensional image plate. Reversible changes in the diffraction pattern included a 28% decrease in intensity of the 14.5 nm meridional reflection, a 12% increase in intensity of 5.9 nm actin layer-line and a somewhat variable 34% increase in intensity of 5.1 nm actin layer-line in laser temperature-jump experiments. When fibres were heated with a temperature ramp, we found that a 70% decrease in intensity of the myosin-related meridional reflection at (14.5 nm)-1 correlated with tension generation. A similar decrease in intensity of the 14.5 nm reflection is seen during tension recovery following a step change in the length of maximally Ca2+ activated fibres. Signals both from actin and actin-bound myosin heads contribute to the 5.1 and 5.9 nm actin layer-lines. Our observed changes in intensity are interpreted as contraction-associated changes in crossbridge shape and/or position on actin.

Actins↗
PubMed1996

Results following secondary intraocular lens implantation in children.

BACKGROUND: Placement of a secondary intraocular lens (IOL) in a child may be considered in children with congenital monocular cataracts who have had complete opacities removed early in life and who later become contact lens intolerant, in eyes that have received trauma which precluded placement of a primary IOL, and in young adults who have bilateral aphakia who become resistant to use of contact lenses or spectacles. METHODS: Clinical records of all children in our practice who received a secondary IOL between January 1988 and December 1994 were reviewed. Indications, biometry, type of procedures, preoperative and postoperative acuity, refractive error, binocular status, and complications were studied. RESULTS: During the 7-year period, 242 cataract operations were performed. Fifty-nine eyes received a lens implant, and 28 of these were secondary implants. There was a mean interval between the initial cataract operation and the procedure for the secondary implant of 77 months. The mean follow-up was 35 months (range, 3 to 71) for the 28 eyes that received a secondary implant. Two received anterior chamber implants. Eight eyes had insufficient capsular support for an IOL. Six implants were placed in the posterior chamber and required suture fixation to the sclera. Twenty of 28 eyes had a measurable improvement in visual acuity. Only 1 eye had a decrease in visual acuity of 2 lines. Fifteen patients (54%) had a final refraction within 1.50 diopters of the fellow eye, and 75% were within 3.00 diopters. During the follow-up period, 2 eyes developed glaucoma. One had a transient pressure elevation, and the second has required 2 filtration procedures. Three patients required a Nd: YAG capsulotomy. Six patients demonstrated Worth fusion at distance and near, but only 3 patients demonstrated 200 seconds of arc or better stereo acuity. CONCLUSION: Placement of contemporary-style, secondary intraocular lenses in children and young adults appears to provide a safe and effective alternative for correction of aphakia in children who become contact lens or spectacle-intolerant.

Adolescent↗
PubMed1996

Transforming growth factor beta expression in the porcine ovary: evidence that theca cells are the major secretory source during antral follicle development.

The transforming growth factors beta (TGF beta) have been implicated as important intrafollicular regulators of follicle development in the mammalian ovary. Recent studies in this laboratory have suggested that, when cultured, both porcine theca and granulosa cells secrete TGF beta, primarily TGF beta 1 (May et al., Endocrine 2:1045-1054, 1994). In this report, evidence is presented that during follicle development in vivo, theca but not granulosa cells are the source of follicular TGF beta. Although both theca and granulosa cells secreted TGF beta when attached to culture dishes, only theca cells secreted detectable levels of TGF beta when cells were cultured in serum-free medium without attachment. Granulosa cells secreted little if any TGF beta. This difference in TGF beta secretion was not found to be due to differences in preparation of the two cell types (i.e., mechanical versus enzymatic preparation). These results suggested that theca cells may be the source of TGF beta in the follicle. To ascertain whether TGF beta is actually secreted by follicles, intact hemi-follicle linings consisting of both theca and granulosa cells were cultured in moderate-term, organ explant culture. Hemi-follicle linings secreted TGF beta at a near linear rate for at least 4 days (approximately 300 pg/follicle/day for 6-8-mm-diameter follicles). The level of TGF beta secretion was directly related to the size of the follicle (p < 0.01). Immunoneutralization studies using TGF beta subtype-specific antibodies indicated that the major form of TGF beta secreted by porcine hemi-follicle linings was TGF beta 1. To further investigate the source of TGF beta during follicle development, a combination of molecular biology procedures was employed. Using 243-bp antisense and sense cRNA probes generated from a simian TGF beta 1 cDNA, we performed in situ hybridization on sections of whole porcine ovaries containing antral follicles. Expression of TGF beta 1 mRNA was localized to both theca and granulosa cells with no expression found in the stroma, suggesting that both cell types transcribe TGF beta 1. TGF beta 1 expression was evaluated additionally by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis. Oligonucleotide primers were generated from the porcine TGF beta 1 cDNA sequence for RT-PCR, and the PCR product (287-bp sequence) was amplified and used for Northern analysis. RT-PCR of total RNA isolated from theca and granulosa cells indicated that both cell types expressed TGF beta 1 mRNA. This finding was confirmed via Northern blot analysis, which further indicated the presence of two TGF beta 1 mRNAs of 2.5 and 3.5 kb, consistent with previous reports of alternate splicing of the porcine TGF beta 1 gene. These data indicate that both cell types express TGF beta 1 mRNA. To further evaluate TGF beta 1 expression, we attempted to isolate TGF beta 1 protein from freshly collected theca and granulosa cells by partial purification and immunoprecipitation. Interestingly, the growth factor could be extracted only from theca cells, not from granulosa cells, despite the presence of mRNA in both cell types. Taken together, these data suggest that whereas both theca and granulosa cells produce the TGF beta 1 gene product, only theca cells translate and secrete the actual growth factor. Thus, it is likely that the theca is the source of the growth factor during follicle development.

Animals↗
PubMed1996

Objective assessment of snoring before and after laser-assisted uvulopalatoplasty.

Laser-assisted uvulopalatoplasty (LAUP) is an outpatient staged surgical procedure for the treatment of snoring. Each patient undergoes a series of procedures with the end point being patient and bed partner satisfaction in most cases. The purpose of this study was to objectively evaluate the frequency, pattern, and volume of snoring in patients prior to and following each LAUP procedure. A sonographic device, SNAP, which records oronasal respiration, was used to assess patients at home. A digital analysis of the frequency, pattern, and volume was then performed. Twenty-seven patients have been completely evaluated with this recording device. The findings demonstrate that the LAUP procedure alters the snoring sound. The maximum, average, and velum-like respiratory noise loudness all showed a statistically significant decrease when comparing the preoperative snoring to the final recording after treatment was completed. In addition, the fundamental frequency of the snoring increased significantly after each LAUP procedure. No change was seen in the snoring index following treatment. These objective results correlated well with the subjective responses of the patients and their bed partners. These findings are consistent with the hypothesis that the LAUP procedure alters snoring in a favorable manner by both objective data and subjective accounts.

Female↗
PubMed1996

Ocular manifestations in Down syndrome.

Down syndrome patients have characteristic ocular findings and associated problems and should have periodic ophthalmologic examinations. The ocular abnormalities of Down syndrome are, for the most part, amenable to treatment and significant visual loss should rarely occur in these patients. Early recognition and treatment will minimize added problems of visual deprivation and permit the patient with Down syndrome to function at his or her highest level of potential.

Child, Preschool↗
PubMed1995

Indirect coupling of phosphate release to de novo tension generation during muscle contraction.

A key question in muscle contraction is how tension generation is coupled to the chemistry of the actomyosin ATPase. Biochemical and mechanochemical experiments link tension generation to a change in structure associated with phosphate release. Length-jump and temperature-jump experiments, on the other hand, implicate phase 2slow, a significantly faster, markedly strain-sensitive kinetic process in tension generation. We use a laser temperature jump to probe the kinetics and mechanism of tension generation in skinned rabbit psoas fibers--an appropriate method since both phosphate release and phase 2slow are readily perturbed by temperature. Kinetics characteristic of the structural change associated with phosphate release are observed only when phosphate is added to fibers. When present, it causes a reduction in fiber tension; otherwise, no force is generated when it is perturbed. We therefore exclude this step from tension generation. The kinetics of de novo tension generation by the temperature-jump equivalent of phase 2slow appear unaffected by phosphate binding. We therefore propose that phosphate release is indirectly coupled to de novo tension generation via a steady-state flux through an irreversible step. We conclude that tension generation occurs in the absence of chemical change as the result of an entropy-driven transition between strongly bound crossbridges in the actomyosin-ADP state. The mechanism resembles the operation of a clock, with phosphate release providing the energy to tension the spring, and the irreversible step functions as the escapement mechanism, which is followed in turn by tension generation as the movement of the hands.

Actomyosin↗
PubMed1995

Force generation and temperature-jump and length-jump tension transients in muscle fibers.

Muscle tension rises with increasing temperature. The kinetics that govern the tension rise of maximally Ca(2+)-activated, skinned rabbit psoas fibers over a temperature range of 0-30 degrees C was characterized in laser temperature-jump experiments. The kinetic response is simple and can be readily interpreted in terms of a basic three-step mechanism of contraction, which includes a temperature-sensitive rapid preequilibrium(a) linked to a temperature-insensitive rate-limiting step and followed by a temperature-sensitive tension-generating step. These data and mechanism are compared and contrasted with the more complex length-jump Huxley-Simmons phases in which all states that generate tension or bear tension are perturbed. The rate of the Huxley-Simmons phase 4 is temperature sensitive at low temperatures but plateaus at high temperatures, indicating a change in rate-limiting step from a temperature-sensitive (phase 4a) to a temperature-insensitive reaction (phase 4b); the latter appears to correlate with the slow, temperature-insensitive temperature-jump relaxation. Phase 3 is absent in the temperature-jump, which excludes it from tension generation. We confirm that de novo tension generation occurs as an order-disorder transition during phase 2slow and the equivalent, temperature-sensitive temperature-jump relaxation.

Animals↗
PubMed1995

Tennis racket shock mitigation experiments.

Measured in this study was the effectiveness of two types of retrofits in mitigating shocks in tennis rackets with ideally high grip fixity. The retrofits were a cushioned grip tape and a string implant device. Three types of rackets were investigated: wood, graphite composite, and metal. For low speed ball impact, neither retrofit changed significantly the magnitude and distribution of e, the coefficient of restitution on the racket heads. For moderate ball speeds impacting the rackets along the vertical centerline, three dynamic racket responses were measured: the free vibration damping based on racket head acceleration, the root-mean-square (rms) grip reaction force, and the fast Fourier transform (FFT) of the grip force. These latter experiments showed that the string implant device had a negligible effect on the three dynamic measures of racket response. However, the cushioned grip tape increased racket damping by up to 100 percent, reduced the rms grip force by about 20 percent, and reduced the magnitude of the FFT of this force by about 40 percent.

Biomechanical Phenomena↗
PubMed1995

Dopa responsive dystonia.

There may be insufficient awareness of dopa responsive dystonia (DRD), which has a characteristic diurnal variation of symptoms. Two children are reported in whom the diagnosis of DRD was missed. The first was thought to have hysteria and the second hereditary spastic paraparesis. A full history is vital for the diagnosis of this important treatable syndrome.

Child↗
PubMed1995

Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer cultures of porcine granulosa cells.

We have examined porcine granulosa cells (pGCs) for the presence of immunodetectable mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinases, ERK) and have further studied the effects of epidermal growth factor (EGF) on the activation of these kinases. Cell lysates prepared from untreated monolayer cultures of pGCs were subjected to Western immunoblotting analysis using monoclonal antibodies to ERK1, ERK2 and pan-specific ERK. MAP kinases were detected having mol wts of 87K (ERK87), 54K (ERK54), 44K (ERK1), and 42K (ERK2). Treatment of pGCs with increasing concentrations (1-10 ng/ml) of EGF for 10 min resulted in electrophoretic mobility shifts of ERK1 and ERK2 suggesting hyperphosphorylation. Immunoprecipitation with an antiphosphotyrosine antibody (PY20), followed by Western analysis using pan-ERK, revealed a marked concentration-dependent increase in tyrosine phosphorylation of ERK2 in response to EGF treatment. The mobility shift and tyrosine phosphorylation of ERK2 was observed as early as 1 min after treatment with 10 ng/ml EGF. In-gel myelin basic protein (MBP) kinase assays revealed significant MBP kinase activity associated with ERK1 and ERK2 in total cell lysates and ERK2 in PY20 immunoprecipitates. Although ERK1 displayed a moderate mobility shift in response to EGF, tyrosine phosphorylation of this MAP kinase was not appreciably increased by EGF. Furthermore, PY20 immunoprecipitates demonstrated minimal MBP kinase associated with ERK1 in response to EGF treatment. Electrophoretic migration, tyrosine phosphorylation, and MBP kinase activity of the ERK54 and ERK87 was not effected regardless of EGF concentration or duration of treatment. These data demonstrate for the first time that pGCs contain immunodetectable MAP kinases. EGF, in a concentration- and time-dependent manner, increases tyrosine phosphorylation and MBP kinase activity (i.e. activation) of ERK2, and to a lesser degree ERK1, suggesting that the activation of MAP kinase may mediate the mitogenic action of EGF in pGCs.

Animals↗
PubMed1995

Advances in the treatment of aortic stenosis across the lifespan.

With these results, the pulmonary autograft constitutes the valve of choice for the left ventricular outflow tract in children of all ages, as well as adolescents and adults. Because there is a growth potential, permanent relief from LVOT obstruction might become possible at any age, especially in the number of infants with critical aortic stenosis who survive a valvotomy or repair of interrupted aortic arch during infancy, but return with multiple level outflow tract obstructions early in childhood. If, however, a child is at risk for developing endocarditis or has a history of cardiac infections, it may be a wise choice to use a homograft initially and replace it later with an autograft when the homograft degenerates.

Age Factors↗