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Biomedical subjects

R E Jones

Publications and source records attributed to R E Jones.

At least 55 records · Page 3Linked to original sources
PubMed1996

Phenotype and function of hematopoietic-derived cells in the CNS of SCID mouse-Lewis rat bone marrow chimeras.

Severe combined immunodeficient (SCID) mice previously transplanted with Lewis rat hematopoietic cells (SCID mouse-Lewis rat chimeras) developed experimental autoimmune encephalomyelitis (EAE) following injection with myelin basic protein (BP)-specific Lewis rat T lymphocytes. Rat T cells did not cause EAE in non-chimeric SCID mice. Thus, in addition to BP-specific rat T cells, transplanted rat hematopoietic cells were involved in the development of EAE in SCID mice. In order to examine the role of hematopoietic rat cells in the development of EAE, chimeras were constructed in SCID mice by transplanting 40 x 10(6) T cell-depleted adult Lewis rat bone marrow cells. Single cell suspensions of brain, blood and spleen from chimeric mice were phenotyped by monoclonal antibody staining specific for mouse or rat cellular differentiation markers at 2 week intervals. Brain cells from chimeric mice were also evaluated for the presence of rat antigen-presenting cells (APC). Four and six weeks after hematopoietic cell transfer, mouse brain contained rat cells expressing the phenotypic markers (CD45+, CD11b/c+) of CNS antigen-presenting cells (APC). Six weeks after hematopoietic cell transfer, rat cells populating the CNS of chimeras were shown to function as APC, stimulating BP-specific Lewis rat T lymphocytes in vitro.

Animals↗
PubMed1996

Ipsilateral parotid sparing study in head and neck cancer patients who receive radiation therapy: results after 1 year.

OBJECTIVE: To determine if three-dimensional treatment planning and conformational dose delivery could minimize radiation dose and salivary gland dysfunction to contralateral parotid glands in patients with unilateral head and neck cancers. STUDY DESIGN: Fifteen patients with unilateral head and neck cancers were treated with three-dimensional treatment planning. Unstimulated and stimulated bilateral parotid saliva was collected before radiotherapy, weekly during treatment, and 1, 3, 6, and 12 months after the completion of radiotherapy. RESULTS: Treated parotid glands received an average dose of 4949 cGy, whereas spared glands received only 355 cGy. Unstimulated and stimulated parotid flow rates decreased dramatically in treated glands after the initiation of radiotherapy and were significantly lower at 1 year after radiotherapy compared with baseline. Conversely, parotid flow rates in spared glands underwent mild changes during radiotherapy and were similar at 1 year after radiotherapy compared with baseline. CONCLUSION: Parotid gland function can be preserved for at least 1 year in patients with unilateral head and neck cancers with three-dimensional treatment planning.

Adult↗
PubMed1996

Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men.

The effect of exogenous androgens on glucose metabolism is controversial. This study was designed to clarify the impact of testosterone enanthate (TE), an aromatizable androgen, and nandrolone decanoate (ND), a nonaromatizable androgen, on glucose disposal. Eleven healthy men were enrolled in a randomized, double-blind cross-over study. All subjects completed two treatment cycles consisting of two weekly injections of placebo followed by six weekly injections of either TE (300 mg/week) or ND (300 mg/week). Treatment periods were separated by a 4-week washout. A tolbutamide-modified, frequently sampled, iv glucose tolerance test was used to assess insulin-dependent and insulin-independent glucose disposal. Data were analyzed using Bergman's minimal model. Parameters examined included acute insulin response to glucose, fasting insulin level, glucose disappearance constant, insulin sensitivity index, glucose effectiveness at basal insulin (SG), and glucose effectiveness at zero insulin (GEZI). Neither androgen adversely affected glucose disposal. To the contrary, treatment with ND actually improved noninsulin-mediated glucose disposal as expressed by SG and GEZI. In ND-treated men, SG (x 10(-2) min(-1)) rose from 2.4 +/- 0.2 at the end of the placebo period to 3.7 +/- 0.6 after treatment (P < 0.05), whereas GEZI (x 10(-2) min(-1)) increased from 1.8 +/- 0.2 to 3.1 +/- 0.6 (P < 0.01). We conclude that the treatment of normal men with supraphysiological doses of either TE or ND does not adversely affect glucose metabolism. Treatment with a nonaromatizable androgen, such as ND, actually improves glucose metabolism by enhancing noninsulin-mediated glucose disposal.

Adult↗
PubMed1996

Metabolic parameters that predict response to clomiphene citrate in obese oligo-ovulatory women.

OBJECTIVE: To determine whether the presence of insulin resistance in obese subjects would adversely affect the rate of ovulation induction by clomiphene citrate. RESULTS: Fasting hyperinsulinemia was associated with the failure to ovulate in response to clomiphene. In addition, other parameters found to correlate with insulin resistance and clomiphene citrate non-response were elevations of total and free testosterone and lower serum sex hormone-binding globulin. CONCLUSIONS: The existence of the presence of endocrine abnormalities associated with hyperinsulinemia and insulin resistance may serve as clinical indicators to help predict which obese patients are likely to respond to clomiphene citrate therapy.

Adult↗
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↗