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Biomedical subjects

R E Jones

Publications and source records attributed to R E Jones.

At least 19 recordsLinked to original sources
PubMed1995

T cells with encephalitogenic potential from multiple sclerosis patients and Lewis rats fail to induce disease in SCID mice following intracisternal injection.

Intracisternal (IC) transfer of cerebrospinal fluid (CSF) mononuclear cells from multiple sclerosis (MS) patients has been reported by others to induce an 'MS-like pathology' in severe combined immunodeficient (SCID) mice. We injected cells from several sources intracisternally into SCID mice and assessed the recipients for clinical and histological disease. CSF cells and myelin basic protein (BP)-specific T lymphocytes from MS patients failed to induce clinical or histological disease following IC injection in SCID mice. Similarly, encephalitogenic BP-specific T cells from Lewis rats were unable to induce disease after IC injection in either SCID mice or Lewis rats, even at cell numbers which induced experimental autoimmune encephalomyelitis in Lewis rats following intraperitoneal (IP) injection. In contrast, naive Lewis rat splenocytes, which were capable of inducing lethal graft-versus-host (GVH) disease following IP transfer in SCID mice, induced paralysis and histopathological changes following IC transfer in SCID mice. We conclude that MS CSF cells do not typically transfer disease into SCID mice following IC injection. Furthermore, it appears likely that neuropathological disease following IC transfer of cells reflects the potential of the transferred cells for inducing GVH disease. Specific recognition of neuroantigens by T cells, as occurs in EAE, is probably not involved in the transfer of paralytic disease by IC transferred MS patient CSF cells.

Animals↗
PubMed1995

Encephalitogenic T lymphocytes develop from SJL/J hematopoietic cells transplanted into severe combined immunodeficient (SCID) mice.

Previously, we constructed chimeras by injecting hematopoietic cells from experimental autoimmune encephalomyelitis (EAE)-susceptible SJL (H-2s) strain mice into severe combined immunodeficient (SCID) C.B-17scid/scid (H-2d) mice. These SCID mouse-SJL mouse hematopoietic cell chimeras developed passive EAE following adoptive transfer of PLP S139-151-specific SJL T lymphocyte line cells, but were resistant to active EAE induced by primary immunization with PLP S139-151. In order to gain an understanding of the encephalitogenic potential of transplanted hematopoietic progenitors in SCID mouse-SJL mouse chimeras, we attempted to induce EAE in hematopoietic chimeras constructed with or without an additional SJL fetal thymus implant. Chimeras with the thymus implant were susceptible to passive and active EAE while chimeras without the thymus implant were susceptible to passive but not active EAE. Encephalitogenic, CD4+, TCR+ T lymphocytes were selected in vitro from PLP S139-151-immunized, thymus-implanted chimeras. These results showed that hematopoietic SJL progenitors developed into antigen-presenting accessory cells and immunocompetent encephalitogenic T lymphocytes following transplantation into SCID mice. The development of primary immune reactivity depended on a fetal thymus implant for expression in SCID mouse-SJL mouse chimeras.

Amino Acid Sequence↗
PubMed1995

Storage-phosphor autoradiography: a rapid and highly sensitive method for spatial imaging and quantitation of radioisotopes.

This study evaluates a storage-phosphor imaging system for rapid autoradiography and quantitation of beta- and gamma-ray emitters in mice. Known quantities of authentic 3H, 14C, and 195mPt (0.06 to 31,714 DPM/mm2) were exposed to imaging plates of the storage-phosphor system for 0.5 min to 15 hr at room temperature. Immediately after exposure, the imaging plates were scanned and the autoradiograms were quantified. Radioactivity as low as 1.8 DPM/mm2 (3H), 0.06 DPM/mm2 (14C) and 3.1 DPM/mm2 (195mPt) was visualized and quantified in 8 hr (3H and 14C) and 6 min (195mPt), respectively. The system displayed a linear range of four to five orders of magnitude (14C: 0.5 to 6,914 DPM/mm2 for 2-hr exposure; 3H: 1.8 to 15,372 DPM/mm2 for 15-hr exposure; and 195mPt: 66 to 198,000 DPM 6 min-exposure). Variation from scan-to-scan was small (< 1% to 5%) and was more pronounced at the lower detection limits and exposure periods. Similar sensitivity, linearity, and variability were obtained in cryosections of murine tumors treated with 14C-fluorouracil or 3H-epinephrine and whole-body autoradiograms of mice treated with 195mPt-cisplatin via liver. The high sensitivity allowed noninvasive imaging of live unanesthetized mice treated with 195mPt with a short exposure time (105 sec). These results validate, for the first time, the high sensitivity, linearity, and wide dynamic range of storage-phosphor technology for quantitative autoradiography of 14C, 3H, and 195mPt isotopes. Storage-phosphor imaging will be useful in rapid quantitative autoradiographic disposition studies of radiolabeled drugs and excipients in vitro and in vivo.

Animals↗
PubMed1995

Major salivary gland flow rates in young and old, generally healthy African Americans and whites.

Saliva is essential to maintain and preserve oral health. Previous studies of primarily white populations demonstrated that salivary gland flow rates are age-stable in healthy adults, but there are little data on African Americans of different ages. The purpose of this study was to determine if there is a relationship between age, gender, and race in unstimulated and stimulated parotid and submandibular salivary gland flow rates and to evaluate subjective responses to questions regarding salivary dysfunction. Sixty generally healthy, middle socioeconomic class African Americans and whites between the ages of 20 to 40 and 60 to 80 years were evaluated. The results indicate, in general, that objective and subjective measurements of major salivary gland flow rates are independent of age, gender, and race. Further studies are required using larger populations. These results suggest that signs and symptoms of dry mouth in the elderly regardless of race or gender should not be considered a normal sequela of aging.

Adult↗
PubMed1994

Target organ-specific up-regulation of the MRC OX-40 marker and selective production of Th1 lymphokine mRNA by encephalitogenic T helper cells isolated from the spinal cord of rats with experimental autoimmune encephalomyelitis.

Lewis x Buffalo F1 rat lymphocytes express both forms of the allelic marker RT7.1 (Lewis) and RT7.2 (Buffalo). We generated myelin basic protein (MBP)-specific encephalitogenic F1 T helper cell lines and adoptively transferred them into naive irradiated Lewis recipients, which enabled us to detect and isolate donor T cells (with RT7.2) within the recipients. The spinal cord and cerebrospinal fluid (CSF) were highly enriched for the donor T cells compared with the blood and spleen. The donor cell number peaked on the first day of disease in the spinal cord and CSF and decreased as the disease progressed. A high percentage of the donor T cells isolated from the spinal cord were positive for the T helper cell activation marker OX-40, whereas a (lower) percentage of CSF donor cells expressed OX-40. Donor cells isolated from blood or spleen were negative for OX-40 expression. In contrast, the IL-2 receptor (CD25) was positive on all the transferred T cells in all tissue sites examined. Cell-sorting experiments showed that the MBP-specific donor cells were enriched for IFN-gamma, IL-2, TNF-alpha, and IL-3 mRNA when compared with the host-recruited spinal cord cells, whereas similar amounts of IL-10 mRNA were produced by both populations. Lymphokine mRNA production was also enriched in donor T cells isolated from the spinal cord compared with donor T cells isolated from the spleen. The spinal cord donor cells produced higher levels of IL-2, IFN-gamma, and IL-3 mRNA, whereas similar amounts of IL-10 and TNF-alpha mRNA were produced from donor cells isolated from the spleen and the spinal cord. Our data suggest that the amount/percentage, activation state, and enhanced lymphokine production at the site of inflammation are all important factors in determining the autoimmune potential of Ag-specific effector T helper cells.

Animals↗
PubMed1994

Effect of 5-alpha-reductase inhibition and dexamethasone administration on the growth characteristics and intratumor androgen levels of the human prostate cancer cell line PC-3.

The endocrine treatment of metastatic prostate cancer includes castration which reliably lowers the serum testosterone (T); however, the effect on intratumor levels of T and dihydrotestosterone (DHT) is less predictable. In vitro work demonstrated that the human prostate cancer cell line PC-3 had significant 5-a-reductase activity that could be inhibited with 17b-N,N-diethylcarbamoyl-4-aza-5a-androstan-3-one (4MA). In this study, we examined the effect of 5-a-reductase inhibition with 4MA and androgen suppression with dexamethasone on the growth characteristics and intratumor androgen levels in the PC-3 cell line in male athymic nude mice (Balb/c). The mice were randomized into six treatment groups: 1) noncastrate vehicle control, 2) 4MA, 0.25 mg/day, 3) 4MA, 1 mg/day, 4) dexamethasone, 25 micrograms/day, 5) 4MA, 1 mg/day, and dexamethasone, 25 micrograms/day, and 6) castrate control group. After 21 days of treatment the animals were sacrificed, serum collected, and tumors harvested. Each treatment produced intratumor DHT levels equivalent to the castrate group. Only the low dose 4MA caused a reduction in intratumor DHT without producing castrate levels of circulating T. The combination of dexamethasone and 4MA was less effective in lowering the intratumor DHT/T ratio than 4MA alone. No significant differences in tumor growth parameters were noted between intact control animals and any of the treatment arms. Serum T levels correlated poorly with intratumor androgen levels. Five-a-reductase inhibition produced castrate levels of intratumor DHT in the nonandrogen-dependent prostate cancer cell line PC-3. The combination of dexamethasone and 5-a-reductase inhibition with 4MA appears to be less effective in lowering intratumor androgen levels than either therapy alone.

5-alpha Reductase Inhibitors↗
PubMed1994

Toxocara canis: failure to find IgE receptors (Fc epsilon R) on eosinophils from infected mice suggests that murine eosinophils do not kill helminth larvae by an IgE-dependent mechanism.

Eosinophils obtained by bronchoalveolar lavage (BAL) from the lungs of mice infected with Toxocara canis were characterized by flow cytometry with respect to cytophilic antibodies and surface Fc receptors. Freshly harvested BAL eosinophils were negative for sIgM, sIgA, sIgE, and Fc epsilon RII. These eosinophils were positive for sIgG1 and Fc gamma RII, although not all Fc gamma RIIs contained bound ligand. Culturing eosinophils for 24 or 48 hr with exogenous IgE and/or IL-4 did not induce IgE binding capacity or Fc epsilon RII expression. IL-4 did not decrease Fc gamma RII expression but did decrease ligand binding capacity by Fc gamma RII. These findings are in marked contrast to the results of studies characterizing the surface of both human and rat eosinophils and may indicate different functional activities for mouse BAL eosinophils in helminth infections.

Animals↗
PubMed1994

Evidence for genetic contamination of inbred buffalo rats (RT-1b) obtained from a commercial vendor.

Inbred Buffalo rats (RT-1b) have been used in studies of experimental autoimmune encephalomyelitis and autoimmune thyroiditis. Since our studies, and those of others, have relied on the genetic purity of inbred Buffalo rats, we chose to test these animals for expression of strain-dependent, allotype-specific variants of CD45 (leukocyte common antigen, LCA) using the monoclonal antibodies RT7.1 and RT7.2. The goal of this study was to confirm the genetic purity and to verify the inbred status of Buffalo rats obtained from a commercial source.

Animals↗
PubMed1994

Human myelin basic protein (MBP) epitopes recognized by mouse MBP-selected T cell lines from multiple sclerosis patients.

We investigated whether myelin basic protein (MBP)-reactive T cells from multiple sclerosis (MS) patients can recognize mouse MBP since this is an expected requirement for the transfer of experimental autoimmune encephalomyelitis (EAE) into severe combined immunodeficiency (SCID) mouse-human chimeras. Peripheral blood mononuclear cells from 11 MS patients were analyzed for in vitro proliferation to mouse MBP. Six patients (55%) responded to mouse MBP at the first or second stimulation. Five T cell lines, selected with mouse MBP from five MS patients, were analyzed for their proliferation to mouse and human MBP and to a panel of synthetic peptides of human MBP. Four of the five lines recognized mouse MBP. In vitro proliferation was restricted by MHC class II in one line tested for MHC restriction. One of the five lines recognized whole human MBP and all five of the lines responded to at least one of the five synthetic peptides corresponding to human MBP residues 8-28, 67-90, 84-102, 87-99 or 130-149. These results show that MS patient T cells recognize mouse MBP and suggest that distinct human MBP epitopes are immunologically cross-reactive with epitopes of mouse MBP.

Amino Acid Sequence↗
PubMed1994

Number and state of rat ovarian mast cells after exogenous administration of luteinizing hormone.

Diestrous rats were treated with an injection of luteinizing hormone (LH), and their ovaries were examined for mast cell number and stage of degranulation at 2 and 4 hr post-injection. LH tripled the number of medullary mast cells at 2 hr. The source or origin of the additional mast cells is unknown. Comparison of the present results with other studies of rat ovarian mast cell dynamics suggests the occurrence of a reduction in mast cell number in early to mid-proestrus followed by an LH-induced increase in late proestrus.

Animals↗
PubMed1994

Refractory period prolongation by biphasic defibrillator waveforms is associated with enhanced sodium current in a computer model of the ventricular action potential.

Mechanisms through which biphasic waveforms lower defibrillation threshold are unknown. Previous work showed that low-intensity biphasic shocks (BS2), delivered during the refractory period of a control action potential (S1), produced significantly longer responses than monophasic shocks (MS2). To test the hypothesis that longer responses are due to hyperpolarization-induced excitation channel recovery during the first portion of the biphasic waveform, we used the Beeler-Reuter ventricular action potential computer model with the Drouhard-Roberge (BRDR) modification to study refractory period stimulation with MS2 (10 msec) and symmetrical BS2 (10 msec each pulse). At 1.5 times diastolic threshold, BS2 prolonged action potential duration when delivered 50 msec into the S1 refractory period, and produced a maximum BS2 versus MS2 response duration difference of 62 msec. Longer BS2 responses corresponded to enhanced BS2-induced sodium current compared to MS2. Maximum BS2 vs MS2 sodium current difference was 400 uA/cm2. These results show that, in a computer model of the ventricular action potential, hyperpolarization by the first phase of a biphasic waveform enhances S2 sodium current and prolongs duration of refractory-period responses. This effectively shortens the cellular refractory period. Prolonged refractory period responses, produced by biphasic defibrillator waveforms, may underlie enhanced defibrillating efficacy at low shock intensities.

Action Potentials↗
PubMed1994

Prophylaxis against infection in total joint arthroplasty. One day of cefuroxime compared with three days of cefazolin.

The efficacy of cefuroxime was compared with the efficacy of cefazolin for prophylaxis against postoperative wound infection in a prospective, double-blind, multicenter study of 1354 patients who had had elective primary or revision total hip or knee arthroplasty. The patients were randomly assigned to receive either 1.5 grams of cefuroxime followed by 750 milligrams eight and sixteen hours later (for a total of one day of antibiotic treatment), or one gram of cefazolin every eight hours for nine doses (for a total of three days of antibiotic treatment). The first dose of each drug was administered fifteen to sixty minutes before the operative incision was made (for a primary operation) or after tissue samples had been obtained for culture (for a revision procedure). After the operation, the patients were assessed daily while hospitalized and then at two to three months and one year after the operation. Demographic characteristics and risk factors were similar in the two groups. For the patients who had had a primary hip arthroplasty, the rate of deep wound infection was 0.5 per cent (one of 187) for those who had received cefuroxime and 1.2 per cent (two of 168) for those who had received cefazolin. For the patients who had had a primary knee arthroplasty, the rate of deep wound infection was 0.6 per cent (one of 178) for those who had received cefuroxime and 1.4 per cent (three of 207) for those who had received cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Treatment of relapsing experimental autoimmune encephalomyelitis with T cell receptor peptides.

Restricted T cell receptor (TCR) VB gene usage by T cells for recognition of antigens involved in the production of experimental autoimmune encephalomyelitis (EAE) offers the possibility of selective immunotherapy. We determined the preferential VB gene usage of lymph node-derived clones from SJL/J mice to recognize the encephalitogenic epitope PLP 139-151 and from PL/J mice to recognize the newly described encephalitogenic epitope PLP 43-64. In addition, the VB gene usage for recognition of PLP 139-151 by T cell lines derived from SJL/J spinal cords was analyzed. Lymph node-derived SJL/J lines and clones specific for PLP 139-151 expressed VB2, VB4, and VB17a preferentially, and PL/J lines and clones specific for PLP 43-64 expressed VB2 and VB8.2 preferentially. A VB4 + SJL/J clone and a VB8.2 + PL/J clone were encephalitogenic. Encephalitogenic SJL/J lines derived from spinal cord expressed VB2, VB10, VB16, and VB17a preferentially, with a predominance of VB2. Candidate TCR peptides were synthesized and tested from the VB gene families VB4, VB8.2, and VB17a, based on our data and previous data on BP-induced EAE in mice. Treatment of relapsing EAE (R-EAE) in SJL/J mice with VB4 and VB17a peptides reduced clinical and histological disease severity, and treatment of R-EAE in (PLxSJL)F1 mice with VB4 and VB8.2 peptides also reduced clinical and histological disease. The use of TCR peptide therapy may have applications for the treatment of human autoimmune diseases such as multiple sclerosis.

Amino Acid Sequence↗