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Biomedical subjects

S Bridges

Publications and source records attributed to S Bridges.

17 recordsLinked to original sources

Modulation of dopamine uptake in rat nucleus accumbens: effect of specific dopamine receptor antagonists and sigma ligands.

The ability of dopamine (DA) antagonists and sigma receptor ligands to alter [(3)H]-DA uptake was examined using synaptosomes prepared from the nucleus accumbens of female rats. Pre-incubation with compounds having a high affinity for sigma (rimcazole, haloperidol, and spiperone) receptors produced dose dependent inhibition of (3)H-DA uptake. Sulpiride, a pure DA D(2) antagonist had no effect. In contrast, DA uptake was potentiated in response to (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, a mixed sigma receptor antagonist and DA D(2) receptor agonist. Similarly, SKF-10,047, a selective sigma receptor agonist, and progesterone, a putative endogenous ligand for the sigma receptor, produced significant increases in (3)[H]-DA uptake. These data suggest a potential role for sigma and DA ligands in the regulation of DA uptake in the nucleus accumbens.

Animals↗

Emergency treatment of neonatal hyperammonaemic coma with mild systemic hypothermia.

An infant aged 3 days presented with hyperammonaemic coma and seizures, which were found to be a result of a urea-cycle defect. Haemofiltration, alternative pathway metabolites, and glucose and insulin failed to lower the plasma ammonia concentration below 2000 micromol/L. The infant was then cooled to a rectal temperature of 34 degrees C for 48 h and put on haemofiltration for 12 h. Plasma ammonia fell to around 100 micromol/L and remained at this concentration after haemofiltration. He roused from his coma, breathed spontaneously, and resumed bottle feeding. Hypothermia may be therapeutic in such instances of metabolic coma because it lowers the enzymatic rate of production of the toxin while non-enzymatic methods remove the toxin.

Ammonia↗

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Brain↗

Conference summary: novel HIV therapies--from discovery to clinical proof of concept.

In this report we have highlighted only a few examples of the extensive efforts underway to better understand the process of HIV pathogenesis, to develop new therapeutic agents to inhibit virus replication, and to identify strategies to restore damage done to the immune system during HIV disease progression. It is expected that progress in these areas will continue to advance, and that development of more effective therapies will lead to comprehensive multifaceted, multipronged treatment regimens.

HIV Infections↗

Frontiers in HIV-1 Therapy: fourth conference of the NIAID National Cooperative Drug Discovery Groups-HIV.

This summary describes current studies in antiviral targeting as reported at the Frontiers in HIV Therapy conference, November 3-7, 1991, in San Diego, California. In parallel with the progressive steps in HIV-1 replication, the meeting covered potential antiviral targets starting from the time HIV-1 docks with the CD4 receptor to virus release. The summary concludes with current research trends to block HIV-1 growth.

Animals↗

Transferrin-like autocrine growth factor, derived from T-lymphoma cells, that inhibits normal T-cell proliferation.

Transferrin, the major iron-binding protein in the plasma of vertebrate species, is an essential growth factor for cells in serum free medium. We have established a cell line, Fr, from peripheral blood mononuclear cells of a patient affected by Sézary syndrome. Fr cells show a very immature antigenic phenotype, while constitutively bearing transferrin receptor on their surface. Furthermore the Fr line does not produce or respond to interleukin 2. Finally its conditioned medium contains both a growth stimulating activity for the Fr cell line and a factor which inhibits T-lymphocyte proliferation. We have identified a protein, produced in large amounts by Fr cells, which shares the immunological properties of human transferrin. Our data suggest that this transferrin-like factor can act as an autocrine growth factor for the producer cells and as an inhibitory factor for normal lymphocytes.

Antigens, Surface↗

Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function.

In an effort to elucidate the role of intrathymic Ia-bearing antigen-presenting cells (APC) on the development of the class II-restricted T cell repertoire, we examined the effect of neonatal anti-I-A treatment on both intrathymic and splenic APC function; on the generation of Lyt-2-,L3T4+, Lyt-2+,L3T4-, and Lyt-2+,L3T4+ T cells; and on the development of class I- and class II-specific T cell functions. Both the thymus and the spleen are completely devoid of Lyt-2-,L3T4+ T cells in young mice treated from birth with anti-I-A, and also lack functions associated with this subset, i.e., alloantigen-specific interleukin 2 production (present report), allo-class II-specific and self-class II-restricted T cell proliferative responses, and helper cell function for the generation of cytotoxic T lymphocyte responses (18). Development of the Lyt-2+,L3T4- subset proceeds undisturbed in these mice, in accord with the previously reported normal levels of cytotoxic T lymphocyte precursors (18). The thymus contains normal numbers of the immature cortical Lyt-2+,L3T4+ cells, indicating that acquisition of the L3T4 marker, in and of itself, is not influenced by anti-I-A treatment. This striking absence of the lineage of T cells responsible for class II-specific T cell functions is correlated with absence of thymic APC function for class II-restricted T cell clones. When anti-I-A-treated mice are allowed to recover from the antibody treatment, splenic and thymic APC function return to normal in 2-3 wk, and thymic Lyt-2-,L3T4+ T cell numbers and functions reappear before such cells are detectable in the spleen. Collectively, these findings suggest that development of the Lyt-2-,L3T4+ lineage of class II-specific T cells is entirely dependent on functional I-A-bearing APC cells in the thymus. In addition, the presence of normal levels of Lyt-2+,L3T4-T cells argues that generation of the two major subsets of T cells (i.e., Lyt-2+,L3T4- and Lyt-2-,L3T4+) occurs through separate events, involving unique sites of interactions between precursor T cells and nonlymphoid major histocompatibility complex-bearing thymus cells.

Animals↗

In vivo treatment of neonatal mice with anti-I-A antibodies interferes with the development of the class I, class II, and Mls-reactive proliferating T cell subset.

In this study we investigated the effect of monoclonal anti-I-A Ab treatment of neonatal mice on the development of alloreactive class I-specific, class II-specific, and Mls-specific T cell proliferative responses. Responses to both class I and class II alloantigens, as well as to Mls antigens, were nearly abrogated at the end of the 2- to 3-wk in vivo treatment period in both the thymus and the spleen. Development of suppressor cells could be excluded as the cause of the observed defect. Diminished responsiveness could not be restored by the addition of IL 2-containing supernatant, suggesting that the reduced T cell proliferative response in anti-I-A-treated mice is due to defective or absent MHC-specific T cell precursors. Furthermore, generation of alloreactive class I-specific proliferative responses was dependent on self-class II recognition, thus providing an explanation for the absence of class I-specific proliferating T cells. Finally, a non-Ia-restricted T cell response, i.e., Con A-induced proliferation, was not affected by anti-I-A Ab treatment. It was previously reported that neonatal anti-Ia Ab treatment results in reduced Ia-antigen expression in the thymus, and that the development of the class I-specific CTL precursors proceeds undisturbed in these mice. The present results extend these findings and suggest that in vivo development of class II-restricted T cells is dependent on interaction with Ia-encoded products on cells either in the thymus or at other sites where T cells undergo development. Moreover, these results demonstrate that in vivo development of the alloreactive class II-specific T cell repertoire is dependent on development of self-class II recognition.

Animals↗

Serum pseudouridine as a biochemical marker in the development of AKR mouse lymphoma.

Pseudouridine is a modified nucleoside derived from the degradation of some species of RNA, primarily transfer RNA, the level of which is elevated in biological fluids of tumor-bearing subjects. In order to study the relationship between pseudouridine levels and the development and progression of neoplasia, we have measured pseudouridine levels in the serum of inbred mice with high (AKR) and low (BALB/c) incidence of spontaneous lymphoma and in mice carrying transplantable lymphoid tumors. Our results show that the serum level of pseudouridine: (a) in healthy mice, is higher in females than in males; (b) increases significantly in female AKR mice in the period preceding the development of lymphoma (preneoplastic period occurring at about 6 months of age); and (c) is highest in AKR mice with lymphoma, the most elevated levels being found in mice with widely disseminated disease. The latter observation was confirmed by experiments with a transplantable AKR lymphoma (T2), where a positive correlation between tumor burden and serum pseudouridine levels was found. On the contrary, in BALB/c mice carrying a transplantable myeloma tumor (MOPC-460), no increase was seen despite the presence of a considerable tumor burden. The increase of pseudouridine in the preneoplastic period, in the absence of overt disease is viewed as an early sign of the development of the disease.

Animals↗

Effect of hydrogen ion buffers on photosynthetic oxygen evolution in the blue-green alga, Agmenellum quadruplicatum.

The photosynthetic oxygen evolution capacity of Agmenelium quadruplication suspended in four hydrogen ion buffers (pH 7.4, 0.05 M) and its synthetic marine growth medium was measured with an oxygen electrode. High rates of oxygen evolution were obtained in the growth medium and N-tris(hydroxymethyl)-methylglycine (Tricine) buffer. Compared to oxygen evolution in the growth medium, rates in phosphate buffer and N-tris(hydroxymethyl)-2-aminoethanesulphonic acid (TES) buffer were sometimes reduced by up to 30% and rates in tris (hydroxymethyl) amino-methane (Tris) were consistently reduced by 50%. An incubation-rinsing procedure caused inhibition of oxygen evolution in TES, phosphate, and Tris by 50 to 100%. Oxygen evolution could be restored to cells rinsed in TES or phosphate by resuspension in growth medium or in buffer plus magnesium and calcium ions. Bezoquinone-supported oxygen evolution was not affected by rinsing with any buffer tested except Tris. Ferricyanide was photoreduced at a low rate by cells rinsed in Tes but at a high rate in TES plus magnesium and calcium ions. We interpreted our results to mean that, in Agmenellum quadruplicatum, inhibition of photosynthetic oxygen evolution by Tris occurs at the level of photosystem 2 while the effects of TES and phosphate are on electron-transport occurring after the rate-limiting reaction.

Buffers↗

Burn patients' pain and anxiety experiences.

The purpose of this study was to examine burn patients' pain and anxiety experiences during resting conditions and procedures. The relationship of contextual factors and interventions to pain and anxiety were also explored. Procedural pain was significantly higher than resting pain (P = .02); however, there were no significant differences in anxiety between resting conditions and procedures (P = .16). There was a significant difference between burn patients' acceptable level of pain, resting pain, and procedural pain (P = .01). Resting pain was significantly lower than patients' acceptable level of pain (P = < .01). Procedural pain was slightly lower than patients' acceptable level of pain, but these results were not statistically significant (P = .37). Percent of total body surface burned was associated with increased procedural anxiety (P = .022). Family presence correlated with decreased procedural pain (P = .011) and midazolam use (P = .047). Prior experience with the procedure was associated with increased morphine(P = .003) and midazolam use (P = .029). These findings support the multifactorial nature of burn pain and anxiety and provide guidance for practice.

Adult↗