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Biomedical subjects

L P Jones

Publications and source records attributed to L P Jones.

At least 19 recordsLinked to original sources
PubMed2001

CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein.

Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokine mimicry for the G glycoprotein of respiratory syncytial virus (RSV) and show binding to CX3CR1--the specific receptor for the CX3C chemokine fractalkine--and induction of leukocyte chemotaxis. We also show that CX3CR1 facilitates RSV infection of cells. Thus, G glycoprotein interaction with CX3CR1 probably plays a key role in the biology of RSV infection.

Animals↗
PubMed2000

Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus.

The innate immune system contributes to the earliest phase of the host defense against foreign organisms and has both soluble and cellular pattern recognition receptors for microbial products. Two important members of this receptor group, CD14 and the Toll-like receptor (TLR) pattern recognition receptors, are essential for the innate immune response to components of Gram-negative and Gram-positive bacteria, mycobacteria, spirochetes and yeast. We now find that these receptors function in an antiviral response as well. The innate immune response to the fusion protein of an important respiratory pathogen of humans, respiratory syncytial virus (RSV), was mediated by TLR4 and CD14. RSV persisted longer in the lungs of infected TLR4-deficient mice compared to normal mice. Thus, a common receptor activation pathway can initiate innate immune responses to both bacterial and viral pathogens.

Animals↗
PubMed1999

N-type calcium channel inactivation probed by gating-current analysis.

N-type calcium channels inactivate most rapidly in response to moderate, not extreme depolarization. This behavior reflects an inactivation rate that bears a U-shaped dependence on voltage. Despite this apparent similarity to calcium-dependent inactivation, N-type channel inactivation is insensitive to the identity of divalent charge carrier and, in some reports, to the level of internal buffering of divalent cations. Hence, the inactivation of N-type channels fits poorly with the "classic" profile for either voltage-dependent or calcium-dependent inactivation. To investigate this unusual inactivation behavior, we expressed recombinant N-type calcium channels in mammalian HEK 293 cells, permitting in-depth correlation of ionic current inactivation with potential alterations of gating current properties. Such correlative measurements have been particularly useful in distinguishing among various inactivation mechanisms in other voltage-gated channels. Our main results are the following: 1) The degree of gating charge immobilization was unchanged by the block of ionic current and precisely matched by the extent of ionic current inactivation. These results argue for a purely voltage-dependent mechanism of inactivation. 2) The inactivation rate was fastest at a voltage where only approximately (1)/(3) of the total gating charge had moved. This unusual experimental finding implies that inactivation occurs most rapidly from intermediate closed conformations along the activation pathway, as we demonstrate with novel analytic arguments applied to coupled-inactivation schemes. These results provide strong, complementary support for a "preferential closed-state" inactivation mechanism, recently proposed on the basis of ionic current measurements of recombinant N-type channels (Patil et al., . Neuron. 20:1027-1038).

Biophysical Phenomena↗
PubMed1999

Prevalence of antibodies to human parvovirus B19 nonstructural protein in persons with various clinical outcomes following B19 infection.

Persistent infections with human parvovirus B19 (B19) associated with debilitating chronic disease have been described, although evidence linking B19 to these more unusual clinical outcomes has been inconclusive. Recent reports have suggested that the development of antibodies to the B19 nonstructural protein (NS1) following B19 infection might be linked to development of severe arthropathy and chronic infection. To confirm these findings, the C-terminal region of the NS1 protein was expressed for use in Western blot assays for detection of anti-NS1 IgG antibodies in human serum. Among 91 persons tested, 0 of 20 not previously infected with B19, 9(36%) of 25 with past B19 infection, and 5 (12.5%) of 40 with recent B19 infection, had detectable anti-NS1 antibodies. Of 6 persons with chronic B19 infection, 2 had detectable antibodies to NS1. The presence of anti-NS1 antibodies did not appear to correlate with unusual clinical outcomes or chronic B19 infection.

Animals↗
PubMed1998

Mechanism of auxiliary subunit modulation of neuronal alpha1E calcium channels.

Voltage-gated calcium channels are composed of a main pore-forming alpha1 moiety, and one or more auxiliary subunits (beta, alpha2 delta) that modulate channel properties. Because modulatory properties may vary greatly with different channels, expression systems, and protocols, it is advantageous to study subunit regulation with a uniform experimental strategy. Here, in HEK 293 cells, we examine the expression and activation gating of alpha1E calcium channels in combination with a beta (beta1-beta4) and/or the alpha2 delta subunit, exploiting both ionic- and gating-current measurements. Furthermore, to explore whether more than one auxiliary subunit can concomitantly specify gating properties, we investigate the effects of cotransfecting alpha2delta with beta subunits, of transfecting two different beta subunits simultaneously, and of COOH-terminal truncation of alpha1E to remove a second beta binding site. The main results are as follows. (a) The alpha2delta and beta subunits modulate alpha1E in fundamentally different ways. The sole effect of alpha2 delta is to increase current density by elevating channel density. By contrast, though beta subunits also increase functional channel number, they also enhance maximum open probability (Gmax/Qmax) and hyperpolarize the voltage dependence of ionic-current activation and gating-charge movement, all without discernible effect on activation kinetics. Different beta isoforms produce nearly indistinguishable effects on activation. However, beta subunits produced clear, isoform-specific effects on inactivation properties. (b) All the beta subunit effects can be explained by a gating model in which subunits act only on weakly voltage-dependent steps near the open state. (c) We find no clear evidence for simultaneous modulation by two different beta subunits. (d) The modulatory features found here for alpha1E do not generalize uniformly to other alpha1 channel types, as alpha1C activation gating shows marked beta isoform dependence that is absent for alpha1E. Together, these results help to establish a more comprehensive picture of auxiliary-subunit regulation of alpha1E calcium channels.

Binding Sites↗
PubMed1997

G-protein modulation of N-type calcium channel gating current in human embryonic kidney cells (HEK 293).

1. Voltage-dependent inhibition of N-type calcium currents by G-proteins contributes importantly to presynaptic inhibition. To examine the effect of G-proteins on key intermediary transitions leading to channel opening, we measured both gating and ionic currents arising from recombinant N-type channels (alpha 1B, beta 1b and alpha 2) expressed in transiently transfected human embryonic kidney cells (HEK 293). Recombinant expression of a homogeneous population of channels provided a favourable system for rigorous examination of the mechanisms underlying G-protein modulation. 2. During intracellular dialysis with GTP gamma S to activate G-proteins, ionic currents demonstrated classic features of voltage-dependent inhibition, i.e. strong depolarizing prepulses increased ionic currents and produced hyperpolarizing shifts in the voltage-dependent activation of ionic current. No such effects were observed with GDP beta S present to minimize G-protein activity. 3. Gating currents were clearly resolved after ionic current blockade with 0.1 mM free La3+, enabling this first report of gating charge translocation arising exclusively from N-type channels. G-proteins decreased the amplitude of gating currents and produced depolarizing shifts in the voltage-dependent activation of gating charge movement. However, the greatest effect was to induce a approximately 20 mV separation between the voltage-dependent activation of gating charge movement and ionic current. Strong depolarizing prepulses largely reversed these effects. These modulatory features provide telling clues about the kinetic steps affected by G-proteins because gating currents arise from the movement of voltage sensors that trigger channel activation. 4. The mechanistic implications of concomitant G-protein-mediated changes in gating and ionic currents are discussed. We argue that G-proteins act to inhibit both voltage-sensor movement and the transduction of voltage-sensor activation into channel opening.

Calcium Channels↗
PubMed1997

Children's and parents' perceptions of children's exposure to violence in urban neighborhoods.

This study examined child and parent perceptions of children's exposure to community violence in a sample of 9 to 12 year olds from high- and low-violence neighborhoods in Washington, DC. More than 75% of the African-American elementary school children sampled indicated that they had witnessed incidents of community violence ranging from homicides to nonfatal shootings, physical assaults, gang violence, robbery with assaults, and rape in their neighborhoods. Yet, almost half of the parents in the study denied that their children had been exposed to any community violence. When these discrepancies were examined, results revealed that children whose parents were in disagreement regarding their exposure to community violence were less likely to experience social support from their peers. Parents' possible lack of awareness as to the experience of their children may place them at further risk by eliminating the possibility for adult-child interaction and guidance regarding their experience with violence in their neighborhoods. Recommendations are provided to assist adults in addressing the needs of children exposed to community violence.

Adolescent↗
PubMed1996

The alpha 1E calcium channel exhibits permeation properties similar to low-voltage-activated calcium channels.

The physiological and pharmacological properties of the alpha 1E calcium (Ca) channel subtype do not exactly match any of the established categories described for native neuronal Ca currents. Many of the key diagnostic features used to assign cloned Ca channels to their native counterparts, however, are dependent on a number of factors, including cellular environment, beta subunit coexpression, and modulation by second messengers and G-proteins. Here, by examining the intrinsic pore characteristics of a family of transiently expressed neuronal Ca channels, we demonstrate that the permeation properties of alpha 1E closely resemble those described for a subset of low-threshold Ca channels. The alpha 1A (P-/Q-type), alpha 1B (N-type), and alpha 1C (L-type) high-threshold Ca channels all exhibit larger whole-cell currents with barium (Ba) as the charge carrier as compared with Ca or strontium (Sr). In contrast, macroscopic alpha 1E currents are largest in Sr, followed by Ca and then Ba. The unique permeation properties of alpha 1E are maintained at the single-channel level, are independent of the nature of the expression system, and are not affected by coexpression of alpha 2 and beta subunits. Overall, the permeation characteristics of alpha 1E are distinct from those described for R-type currents and share some similarities with native low-threshold Ca channels.

Animals↗
PubMed1993

Protozoal abortion in a herd of cattle concurrently infected with Hammondia pardalis.

Protozoal infection was diagnosed as the cause of abortion in a large drylot dairy herd located in northeastern Mexico. Diagnosis was made on the basis of finding encephalitis, myocarditis, protozoal cysts, and protozoal tachyzoites in aborted fetuses. The blended ration fed to the cows had been contaminated by the feces of a large resident population of feral domestic cats that used components of the blended ration for den sites (stored hay) or as a latrine (grain). The cows that aborted contained tissue phases of a protozoan infective for domestic cats. The morphologic features of the oocyst and biologic features of the protozoan were identical to those of Hammondia pardalis.

Abortion, Veterinary↗
PubMed1990

Naturally occurring apicomplexan acute interstitial pneumonitis in thick-billed parrots (Rhynchopsitta pachyrhyncha).

This report describes acute interstitial pneumonitis due to an apicomplexan parasite with schizogony in endothelial cells of pulmonary vessels accompanied by early and metrocyte stages of sarcocysts in the heart of a thick-billed parrot (Rhynchopsitta pachyrhyncha). The pattern of this disease is similar to that of the acute phase (approximately 10-15 days postinoculation) of experimental infections of budgerigars, Melopsittacus undulatus, with high doses of sporocysts of Sarcocystis falcatula.

Acute Disease↗
PubMed1988

Hepatozoon sp. in wild carnivores in Texas.

Twelve coyotes (Canis latrans), three bobcats (Lynx rufus) and six ocelots (Felis pardalis) from the Gulf Coast of Texas were infected with Hepatozoon sp. The geographic distribution of infected wild animals coincides with the highest prevalence of Hepatozoon canis infection in domestic dogs for which the wild species may act as a reservoir.

Animals↗
PubMed1988

Bilateral kidney translocation in sheep.

Bilateral kidney translocation was performed on 7 adult sheep. In each sheep, we took 9 renal biopsy specimens (40 mg each) percutaneously between 36 and 110 days after surgery. The serum urea nitrogen and creatinine concentrations remained normal, at least through postoperative day 66 (7 biopsy specimens). The 7 sheep were euthanatized and necropsied 113 days after surgery; 75 to 90% of each kidney was normal. The only abnormal areas of each kidney were attributable to resolving biopsy lesions. This surgical model may allow for fewer animals to be used for tissue residue or nephrotoxicity studies.

Abdomen↗
PubMed1987

Experimentally induced Cassia roemeriana poisoning in cattle and goats.

The dried, ground aerial portions of the plant Cassia roemeriana were administered to each of seven calves at a dosage of 10 g/kg of body weight/day for 2 to 10.5 days and to each of six goats at a dosage of 10 g/kg/day for 5 days or 5 or 7 g/kg/day for 23 to 25 days. Experimentally induced C roemeriana poisoning in both species resulted in hepatopathic poisoning characterized by a brief survival period (3.9 to 7.9 days), moderate-to-severe hepatocellular damage, and little or no evidence of injury to skeletal muscle or resulted in myopathic poisoning characterized by a longer period of survival, mild-to-severe skeletal myopathy, and mild hepatocellular injury. The minimal dosage that induced hepatopathic poisoning (also the minimal lethal dosage) was 10 g/kg/day for 3 days in calves and for 5 days in goats. The minimal dosage that induced the myopathic syndrome (as determined by the earliest increase in serum creatine kinase activity) was 10 g/kg/day for 6 days for calves and 5 g/kg/day for 10 to 16 days for goats.

Animals↗
PubMed1986

Dermal leishmaniasis in a Texas cat.

Leishmaniasis was diagnosed by demonstrating amastigotes of Leishmania from dermal lesions on the ear of a male long-haired domestic cat from Uvalde, Texas. Leishmania from the cat were propagated in Syrian hamsters, bovine macrophages, and in NNN medium. The organism, in the L. mexicana complex, is apparently the same as that reported from recent human cases in the same area.

Animals↗
PubMed1984

Primary hyperparathyroidism in German shepherd dogs: a disorder of probable genetic origin.

Primary hyperparathyroidism was diagnosed in two German shepherd pups from a litter of four females. Clinical signs were apparent by two weeks of age and included stunted growth, muscular weakness, and polydipsia/polyuria. Radiography revealed diffuse reduction in bone density. Both pups had marked hypercalcemia, hypophosphatemia, increased plasma immunoreactive parathyroid hormone concentrations and increased fractional clearance of inorganic phosphate in the urine. Intravenous infusion of one affected pup with calcium gluconate failed to suppress the plasma concentration of immunoreactive parathyroid hormone, suggesting autonomous secretion of parathyroid hormone. Necropsy of the other pup at eight weeks of age revealed diffuse hyperplasia of parathyroid chief cells, nodular hyperplasia of thyroid C-cells, skeletal alterations consistent with fibrous osteodystrophy, hypercalcemic nephropathy, and extensive mineralization of the lungs and gastric mucosa. The dam and sire were half sibs. One male pup from a previous litter of six had developed similar clinical signs and radiographic lesions, suggesting autosomal recessive inheritance. This is the first report of hereditary primary hyperparathyroidism in domestic animals, a disease which may be analogous to hereditary neonatal primary hyperparathyroidism in children.

Animals↗
PubMed1984

1,3 Butanediol treatment of ethylene glycol toxicosis in dogs.

In order to assess the therapeutic value of 1,3 butanediol in ethylene glycol toxicosis, mixed-bred dogs were given an oral dose of commercial antifreeze at 6 ml/kg of body weight (0 hour) and treated (IV) 7 times at 6-hour intervals with 5.5 ml/kg of body weight 1,3 butanediol solution (20% in physiological saline solution) beginning at 8, 12, and 21 hours. Serum glycolic acid concentration was quantitated by high-pressure liquid chromatography. Three dogs that were given ethylene glycol, but no 1,3 butanediol treatment, died with elevated serum glycolic acid concentrations. Five dogs were given ethylene glycol and 1,3 butanediol treatment. Of 2 dogs treated at 8 hours, 1 survived and 1 died at 39 hours; 1 treated at 12 hours and 1 treated at 21 hours survived; 1 dog died soon (27 hours) after treatment was initiated at 21 hours. Four of the 5 dogs had dramatically decreased serum glycolic acid concentrations after 1,3 butanediol treatment, indicating its effectiveness in inhibiting alcohol dehydrogenase-dependent glycolic acid formation in vivo.

Animals↗
PubMed1983

Isolation of an anticomplement factor from the venom of the Mojave rattlesnake (Crotalus scutulatus scutulatus).

The venom of the Mojave rattlesnake was fractionated by DEAE-Sephadex column chromatography. A venom fraction, F5, inactivated both human and guinea pig complement. Both serum and purified C3 were partially converted to a protein of faster electrophoretic mobility, indicating that F5 had a direct proteolytic effect on C3. This product was capable of passively lysing guinea pig red blood cells. F5 very effectively inactivated the classical pathway, but only partially inactivated the alternative pathway. The venom fraction worked in a dose-dependent fashion, was heat labile but not lethal to mice at concentrations as high as 10 micrograms/g mouse weight. Antibodies were produced by immunizing rabbits with F5. The antibodies formed one precipitin line in gels against F5 and also neutralized the complement inactivating activity. The antibodies recognized the venom of the western diamondback rattlesnake, Crotalus atrox, but did not, however, recognize the crude venom of the Mojave rattlesnake.

Animals↗