Biomedical subjects

Richard E Jones

Publications and source records attributed to Richard E Jones.

At least 19 recordsLinked to original sources

PubMed2006

Uterine motility in the reptile Anolis carolinensis: interactive effects of tension, prostaglandins, calcium, and vasotocin.

Uteri of Anolis carolinensis exhibited spontaneous rhythmic contractions in vitro. Addition of arginine vasotocin (AVT) caused an immediate, strong, tonic contraction followed by rhythmic contractions with the same frequency as spontaneous contractions but of a greater amplitude. At low tension (1.5 g) the AVT-induced tonic contraction was blocked by low dose of indomethacin, suggesting that it is influenced by calcium rather than prostaglandins (PGs). An increase in tension (from 1.5 to 15 g) reduced the duration of the AVT-induced tonic contraction; this stretch-induced decrease was also blocked by indomethacin. Stretch also decreased the duration of the rhythmic contractions, but this stretch effect was not inhibited by indomethacin. The rest interval between rhythmic contractions was decreased by PGF2alpha and PGE2, and indomethacin or stretch blocked these PG effects. Indomethacin, AVT, or stretch alone did not affect PGF2alpha secretion from AVT-treated uteri. Stretch also reduced PGF2alpha secretion from AVT-treated uteri, an effect inhibited by indomethacin.

Animals↗

PubMed2006

Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice.

Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Here, the effects of the antioxidant, alpha-lipoic acid (ALA) were tested on the Tg2576 mouse, a transgenic model of cerebral amyloidosis associated with AD. Ten-month old Tg2576 and wild type mice were fed an ALA-containing diet (0.1%) or control diet for 6 months and then assessed for the influence of diet on memory and neuropathology. ALA-treated Tg2576 mice exhibited significantly improved learning, and memory retention in the Morris water maze task compared to untreated Tg2576 mice. Twenty-four hours after contextual fear conditioning, untreated Tg2576 mice exhibited significantly impaired context-dependent freezing. ALA-treated Tg2576 mice exhibited significantly more context freezing than the untreated Tg2576 mice. Assessment of brain soluble and insoluble beta-amyloid levels revealed no differences between ALA-treated and untreated Tg2576 mice. Brain levels of nitrotyrosine, a marker of nitrative stress, were elevated in Tg2576 mice, while F2 isoprostanes and neuroprostanes, oxidative stress markers, were not elevated in the Tg2576 mice relative to wild type. These data indicate that chronic dietary ALA can reduce hippocampal-dependent memory deficits of Tg2576 mice without affecting beta-amyloid levels or plaque deposition.

Aging↗

PubMed2006

The infected knee: all my troubles now.

Infection after total knee arthroplasty poses formidable challenges to the surgeon. Once an infection is diagnosed, the identification of the organism and its sensitivity to antibiotics is essential. The host's healing capacity is vital. Supplemental nutrition and cessation of smoking can improve wound healing. Surgical goals include debridement of necrotic tissue and elimination of the dead space. Intravenous antibiotics and a 2-stage protocol are the standard of care. At our institution, the first stage is performed with an implant and antibiotic-cement composite. This articulating spacer maintains limb length and tissue compliance. The patient can maintain a functional status between stages. Definitive reconstruction is more readily accomplished with this method in contrast to the static spacer approach. The clinical efficacy of this protocol has been well documented in the literature.

Aged↗

PubMed2006

Rotating platform knees: an emerging clinical standard: in the affirmative.

Total knee arthroplasty (TKA) is one of the most frequently performed reconstructive operations in the world today. It has been extended to younger and more active patients. Wear at the articulation and fixation loosening are the principle modes of TKA failures. Data from clinical follow-up, laboratory testing, and in vivo kinematic motion analysis have all demonstrated excellent biomechanics, wear characteristics, and fixation durability with mobile-bearing TKA designs. This review summarizes some of the most recently published data in the efficacy of rotating platform TKAs.

Arthroplasty, Replacement, Knee↗

PubMed2006

What would you do? Case challenges in knee surgery.

Six cases representing a variety of orthopedic issues were presented to a panel of senior surgeons. These included the following: (1) developmental patella baja with degenerative arthritis, (2) high valgus knee with attenuated medial collateral ligament, (3) degenerative arthritis with near-ankylosis, (4) depressed tibial plateau fracture with degenerative arthritis, (5) degenerative arthritis with laterally dislocating patella, and (6) degenerative arthritis with distal femoral malunion.

Aged↗

PubMed2006

Comparison of two delivery methods of local anesthetic distribution after intra-articular knee injection.

We studied the intra-articular distribution of radiopaque dye to compare the efficacy of a continuous low-volume infusion with an intermittent high-volume bolus infusion. Knee arthroscopy patients were randomized with 10 cc of dye infused over 2.5 hours versus 10 cc bolus of dye. Radiographs were independently evaluated. Eleven knees (low-volume infusion) filled an average of 3 of 7 compartments, while 10 knees (bolus group) had complete filling of all seven compartments (P < .001). This study supports high-volume bolus injections of local anesthetics to achieve consistent distribution to all knee compartments while enhancing pain control.

Adult↗

PubMed2006

High-flexion rotating-platform knees: rationale, design, and patient selection.

High flexion in total knee arthroplasty (TKA) is any flexion beyond 125 degrees. High-flexion activities such as kneeling or praying are done with internal rotation, external rotation, and in neutral. Therefore, maximum flexion TKA requires a rotating platform. Superior range of motion (ROM) and fluoroscopic kinematics of femoral roll-back have been shown with the P.F.C. Sigma RP posterior-stabilized knee. This knee was modified to reduce the P.F.C. Sigma RP-F, a maximum flexion knee, by adding a third contact area at the post-cam mechanism to significantly increase bearing conformity and decrease polyethylene stresses in the range of 125 degrees-155 degrees. Clinical experience is reported with statistically significant increases in postoperative ROM in patients with the P.F.C. Sigma RP-F. Patient selection criteria for the P.F.C. Sigma RP-F include patients with high-flexion lifestyles, younger, more active patients demanding a better ROM, and those patients with less than 100 degrees preoperative ROM. This knee system shows significant promise in providing maximum flexion, and system longevity is expected.

Humans↗

PubMed2006

Total knee arthroplasty with modular rotating-platform hinge.

Third-generation modular rotating hinged knee systems are now widely available. The S-ROM rotating hinge features slotted and splined stems for torsional stability, and metaphyseal filling and loading sleeves for the bony defects encountered in revision total knee arthroplasty (TKA). Primary indications for a hinge include medial or lateral collateral loss, massive bone loss, and metaphysis and cortical shell, which includes collateral origins or insertions, and severe flexion gap imbalance requiring a link system for stability. Indications for a hinge in primary TKA include patients with neuromuscular deficits such as polio or flail knee, who require the hyperextension stop. Reported midterm results are excellent with no mechanical failures and positive bone remodeling in 65 patients.

Arthroplasty, Replacement, Knee↗

PubMed2005

Analysis of 16 retrieved proximally cemented femoral stems.

Sixteen proximally cemented, collared, and distally splined, Bridge Hip femoral stems with a matte proximal surface and smooth distal surface were retrieved because of loosening. Electron microscopy, with correlated elemental analysis, identified titanium particulate embedded in the internal surface of the cement mantle. Data supported the observations that loosening of the femoral stems was related to proximal debonding at the cement-implant interface, loosening at the proximal cement-bone interface, and inherent rotational instability. Cement-implant interface debonding resulted in the proximally matte femoral stem surface abrading with the opposing cement mantle, resulting in particulate and osteolysis in some cases. Careful consideration of implant design and clinically relevant biomechanical testing protocols should be considered before the clinical introduction of future proximally cemented femoral stems.

Adult↗

PubMed2005

Mobile bearings in revision total knee arthroplasty.

Mobile-bearing hinged knee replacement systems were used early on for primary and revision knee arthroplasty, but they were associated with high failure rates. Third-generation modular rotating platform hinged knee replacement systems have evolved with modular diaphyseal engaging slotted and splined stems and metaphyseal filling and loading sleeves. Additionally, significant improvement of the articulation between the rotating hinge mechanism and tibial component with broad congruent surfaces has decreased the deleterious stresses that contributed to the failures of earlier designs. The excellent mid-term results of the S-ROM modular mobile-bearing hinge and modular rotating plaform nonlinked knee replacement systems provide solid evidence for expanding the indications for rotating platform revision systems.

Arthroplasty, Replacement, Knee↗

PubMed2004

HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes.

Susceptibility to multiple sclerosis (MS) is associated genetically with human leucocyte antigen (HLA) class II alleles, including DRB1*1501, DRB5*0101, and DQB1*0602, and it is possible that these alleles contribute to MS through an enhanced ability to present encephalitogenic myelin peptides to pathogenic T cells. HLA-DRB1*1502, which contains glycine instead of valine at position 86 of the P1 peptide-binding pocket, is apparently not genetically associated with MS. To identify possible differences between these alleles in their antigen-presenting function, we determined if T-cell responses to known DRB1*1501-restricted myelin peptides might be diminished or absent in transgenic (Tg) DRB1*1502-expressing mice. We found that Tg DRB1*1502 mice had moderate to strong T-cell responses to several myelin peptides with favorable DRB1*1501 binding motifs, notably myelin oligodendrocyte glycoprotein (MOG)-35-55 (which was also encephalitogenic), proteolipid protein (PLP)-95-116, and MOG-194-208, as well as other PLP and MOG peptides. These peptides, with the exception of MOG-194-208, were also immunogenic in healthy human donors expressing either DRB1*1502 or DRB1*1501. In contrast, the DRB1*1502 mice had weak or absent responses to peptides with unfavorable DRB1*1501 binding motifs. Overall, none of the DRB1*1501-restricted myelin peptides tested selectively lacked immunogenicity in association with DRB1*1502. These results indicate that the difference in risk association with MS of DRB1*1501 versus DRB1*1502 is not due to a lack of antigen presentation by DRB1*1502, at least for this set of myelin peptides, and suggest that other mechanisms involving DRB1*1501 may account for increased susceptibility to MS.

Amino Acid Sequence↗

PubMed2004

Specificity of regulatory CD4+CD25+ T cells for self-T cell receptor determinants.

Although the phenotypic and regulatory properties of the CD4(+)CD25(+) T cell lineage (Treg cells) have been well described, the specificities remain largely unknown. We demonstrate here that the CD4(+)CD25(+) Treg population includes the recognition of a broad spectrum of human TCR CDR2 determinants found in the germline V gene repertoire as well as that of a clonotypic nongermline-encoded CDR3beta sequence present in a recombinant soluble T cell receptor (TCR) protein. Regulatory activity was demonstrated in T cell lines responsive to TCR but not in T cell lines responsive to control antigens. Inhibitory activity of TCR-reactive T cells required cell-cell contact and involved CTLA-4, GITR, IL-10, and IL-17. Thus, the T-T regulatory network includes Treg cells with specificity directed toward self-TCR determinants.

Antibodies, Blocking↗

PubMed2004

T lymphocytes do not directly mediate the protective effect of estrogen on experimental autoimmune encephalomyelitis.

Gender influences mediated by 17 beta-estradiol (E2) have been associated with susceptibility to and severity of autoimmune diseases such as diabetes, arthritis, and multiple sclerosis. In this regard, we have shown that estrogen receptor-alpha (Esr1) is crucial for the protective effect of 17 beta-estradiol (E2) in murine experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis. The expression of estrogen receptors among various immune cells (eg, T and B lymphocytes, antigen-presenting cells) suggests that the therapeutic effect of E2 is likely mediated directly through specific receptor binding. However, the target immune cell populations responsive to E2 treatment have not been identified. In the current study, we induced EAE in T-cell-deficient, severe combined immunodeficient mice or in immunocompetent mice with encephalitogenic T cells from wild-type Esr1+/+ or Esr1 knockout (Esr1-/-) donors and compared the protective E2 responses. The results showed that E2-responsive, Esr1+/+ disease-inducing encephalitogenic T cells were neither necessary nor sufficient for E2-mediated protection from EAE. Instead, the therapeutic response appeared to be mediated through direct effects on nonlymphocytic, E2-responsive cells and down-regulation of the inflammatory response in the central nervous system. These results provide the first demonstration that the protective effect of E2 on EAE is not mediated directly through E2-responsive T cells and raise the alternative possibility that nonlymphocytic cells such as macrophages, dendritic cells, or other nonlymphocytic cells are primarily responsive to E2 treatment in EAE.

Animals↗

PubMed2004

Modular revision stems in total hip arthroplasty.

Many different clinical circumstances are seen in revision total hip arthroplasty. Modular stems provide significant flexibility in choices to ensure distal and/or proximal unitary construct of implant and host bone. There are two basic types of modular stems. Designs that incorporate a metaphyseal sleeve taper fit with a splined, slotted distal body of varying lengths and neck offsets and also provide infinite choices for version of the components. Designs incorporate a distal stem with various proximal stems and Morse tapers. These designs also may vary the distal stem configuration from extensively porous-coated, to tapered and with corundum, to splined and slotted. Although there have been no clinical studies that document improved outcomes with modular stems over one-piece stems, the intraoperative flexibility provided by choices of diameter, stem length, fixation type, and proximal stem size and orientation enable establishment of a stable hip center. I will review the clinical indications for modular stems, outline their advantages, discuss the applicable operative techniques, the reported results, and the limitations of the current literature.

Arthroplasty, Replacement, Hip↗

PubMed2003

Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity.

CD4+CD25+ regulatory T cells (Treg cells) prevent T cell-mediated autoimmune diseases in rodents. To develop a functional Treg assay for human blood cells, we used FACS- or bead-sorted CD4+CD25+ T cells from healthy donors to inhibit anti-CD3/CD28 activation of CD4+CD25- indicator T cells. The data clearly demonstrated classical Treg suppression of CD4+CD25- indicator cells by both CD4+CD25(+high) and CD4+CD25(+low) T cells obtained by FACS or magnetic bead sorting. Suppressive activity was found in either CD45RO- (naive) or CD45RO+ (memory) subpopulations, was independent of the TCR signal strength, required cell-cell contact, and was reversible by interleukin-2 (IL-2). Of general interest is that a wider sampling of 27 healthy donors revealed an age- but not gender-dependent loss of suppressive activity in the CD4+CD25+ population. The presence or absence of suppressive activity in CD4+CD25+ T cells from a given donor could be demonstrated consistently over time, and lack of suppression was not due to method of sorting, strength of signal, or sensitivity of indicator cells. Phenotypic markers did not differ on CD4+CD25+ T cells tested ex vivo from suppressive vs. nonsuppressive donors, although, upon activation in vitro, suppressive CD4+CD25+ T cells had significantly higher expression of both CTLA-4 and GITR than CD4+CD25- T cells from the same donors. Moreover, antibody neutralization of CTLA-4, GITR, IL-10, or IL-17 completely reversed Treg-induced suppression. Our results are highly consistent with those reported for murine Treg cells and are the first to demonstrate that suppressive activity of human CD4+CD25+ T cells declines with age.

Adult↗

PubMed2003

CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis.

Transgenic mice with T-cell receptor (TCR) specific for myelin basic protein (MBP)-Ac1-11 peptide and homozygous for the RAG-1 mutation (T/R- mice) spontaneously develop acute progressive experimental autoimmune encephalomyelitis (Sp-EAE) mediated by CD4+ T cells. Microarray analysis of spinal cord tissue obtained from symptomatic versus non-symptomatic T/R- mice revealed strongly upregulated transcripts for genes involved in antigen presentation and processing, signal transduction, transcription regulation, metabolism, development, cell cycle, and many other processes involved in the induction of clinical and pathological signs of Sp-EAE. Several highly expressed genes were related directly to inflammation, including cytokines/receptors, chemokines/receptors, acute phase, complement molecules, and others. Many CNS-specific genes were also upregulated in sick mice. Abundance of message for the Tg TCR BV8S2 gene as well as several monocyte/macrophage-associated genes would suggest that both components play a crucial role in the pathogenesis of Sp-EAE. The profile of transcriptional changes found during the development of Sp-EAE provides the first description of the encephalitogenic process in the absence of purposeful immunization with myelin peptides and immune-enhancing adjuvants. This unique approach is the first to implicate molecules and pathways that contribute naturally to onset of paralysis and demyelination, and thus may provide unique insights and novel treatment strategies for human diseases such as multiple sclerosis.

Animals↗

PubMed2003

Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis.

The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires. Consequently, the precise nature of a causal relationship between epitope spreading and disease progression remains uncertain. To determine whether relapsing or progressive EAE can occur in the absence of epitope spreading, we evaluated the course of disease in mice which possessed only a single myelin-specific TCR. These mice (transgenic/SCID +/+) exhibited a progressive and sometimes remitting/relapsing disease course in the absence of immune reactivity to multiple, spreading myelin epitopes. The results provide direct experimental evidence relevant to discussions on the mechanisms of disease progression in MS and EAE.

Adoptive Transfer↗

PubMed2003

Nonmyelin-specific T cells accelerate development of central nervous system APC and increase susceptibility to experimental autoimmune encephalomyelitis.

Previously we demonstrated that both myelin-specific and nonmyelin-specific rat T cells were capable of accelerating the development of transplanted rat BM-derived APC in the CNS of SCID C.B-17/scid (SCID) mice. This suggested that nonmyelin-specific T cells might be capable of increasing susceptibility to EAE by increasing the number and function of APC in the CNS before disease induction. To assess this possibility, we evaluated disease incidence, day of onset, duration, mean peak severity, cumulative disease index, and histopathology in the presence or absence of nonmyelin-specific T cells. The results demonstrate an association between T cell responses to nonmyelin Ags, accelerated development of BM-derived CNS APC before disease induction, and heightened susceptibility to CNS inflammation mediated by myelin-specific T cells. This suggests that T cell responses to nonmyelin Ags can potentiate CNS inflammation by elevating the functional presence of CNS APC.

Animals↗