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R Stead

Publications and source records attributed to R Stead.

11 recordsLinked to original sources
PubMed1992

A comparison of therapeutic schedules for administering granulocyte colony-stimulating factor to nonhuman primates after high-dose chemotherapy.

Granulocyte colony-stimulating factor (G-CSF) has been shown to be effective in clinical trials for reducing the period of neutropenia after chemotherapy. In this study, we compared the timing for initiating G-CSF administration after chemotherapy with the duration of neutropenia and hematopoietic regeneration. Nonhuman primates treated with high-dose chemotherapy (mechloroethamine, 1.5 mg/kg, intravenously) and not administered G-CSF therapy experienced 8 days of neutropenia (absolute neutrophil count [ANC] less than 1,000/mm3) and had an ANC nadir of 124 +/- 64/mm3 at day 7. Monkeys receiving G-CSF (5 micrograms/kg/d, subcutaneously) began treatment on either days 1, 3, 5, or 7 after chemotherapy. Monkeys treated with G-CSF had an earlier ANC recovery and the number of days with an ANC less than 500/mm3 and ANC less than 1,000/mm3 was reduced by approximately 50% in all treatment strategies. All G-CSF-treated animals, irrespective of the time that G-CSF was initiated, reached an ANC of 10,000/mm3 on day 13 +/- 1 day after chemotherapy. These results demonstrated that the duration of G-CSF therapy was almost twice as long for monkeys treated on day 1 as it was for monkeys that received therapy beginning on day 7. A comparison of the results for all treated monkeys identified a distinct difference in the responses of monkeys treated on day 1 from that of animals treated with G-CSF at later times. G-CSF initiated 1 day after chemotherapy led to an earlier onset of neutropenia and a more rapid and augmented recovery of myeloid progenitor cells in the peripheral blood when compared with control and delayed therapy groups. This study demonstrates that neutropenia due to a single dose of mechloroethamine can be equally reduced with both early and delayed initiation of G-CSF. Further, initiating G-CSF therapy after 7 days required approximately 50% less days of therapy to reach an appropriate termination point. The applicability of these findings to other chemotherapy regimens and for repeated cycles is uncertain and needs to be further evaluated. This is a US government work. There are no restrictions on its use.

Animals↗
PubMed1992

A behavioral profile of autoimmune lupus-prone MRL mice.

Manifestations of the human autoimmune disease systemic lupus erythematosus (SLE) include a number of behavioral and cognitive deficits. The present study asks whether neurobehavioral dysfunction is present also in MRL mice that spontaneously develop most of the fundamental immunological aberrations of SLE. There are two congenic substrains of MRL mice that differ in the time of disease onset: MRL-lpr mice develop lupus early and MRL(-)+/+ develop the typical signs of disease relatively late in life. The behavior of these substrains was assessed at 7 to 11 weeks of age, a time that coincides with the onset of disease in MRL-lpr mice and the absence of known lupus symptoms in the MRL(-)+/+ group. When compared to the congenic MRL(-)+/+ control substrain, MRL-lpr mice were spontaneously less active, traversed a crossbeam slower, and ceased responding to the novelty of a new environment sooner. They were also more reluctant to leave their home base or travel far away from it and perseverated in their response bias during extinction and reversal learning. Immunological status was characterized by moderate proteinuria in both substrains and high titers of antinuclear antibodies in MRL-lpr but not MRL(-)+/+ mice. Histological analysis revealed minimal or no signs of joint pathology in MRL-lpr mice. Thus, this study shows the presence of behavioral dysfunction in mice with early stages of autoimmune disease and gives support for the idea that MRL mice may provide a useful model of neurobehavioral dysfunction in SLE. It is suggested that the behavioral profile of MRL-lpr mice may indicate increased "timidity," related to genetics, autoimmunity, or both.

Animals↗
PubMed1990

S100 protein expression in human melanoma cells: comparison of levels of expression among different cell lines and individual cells in different phases of the cell cycle.

The synthesis of S100 protein in cultured human melanoma cells was examined using metabolic labeling with [35S]methionine, immunoprecipitation with anti-S100 protein antiserum, and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Six of seven cell lines derived from melanomas synthesized relatively large amounts of S100 protein, whereas three cell lines derived from normal melanocytes synthesized lesser amounts. Synthesis of S100 protein was not detected in 10 human cell lines of nonneuroectodermal origin. Analysis of poly(A+) RNA from one melanoma cell line by Northern blot hybridization with a probe specific for the beta subunit of rat S100 protein revealed a single mRNA species of 1.0 kb coding for the human protein. Flow cytometric analysis of individual cells of two melanoma cell lines and the rat glioma cell line C6 indicated that G0/G1 cells were heterogeneous with respect to S100 protein expression, while almost all the cells in S + G2 + M expressed S100 protein. These results suggest that expression of S100 protein in G0/G1 could be a prerequisite for progression of the cells through the cell cycle.

Blotting, Northern↗
PubMed1989

Significance and value of immunohistochemical localization of pregnancy specific proteins in feto-maternal tissue throughout pregnancy.

Tissue from 50 cases of products of conception and placenta at different gestational ages from as early as 12 d post ovulation up to 40 wk were examined by immunoperoxidase technique for localization of HCG, HPL, SP1, and PAPP-A. HCG was localized in the cytoplasm of syncytiotrophoblast (ST) with strong intensity in the 12-d blastocyst and remained strong until 8 to 10 wk. It then gradually decreased, becoming almost negative in term placenta. HCG was also seen in the cytoplasm of intermediate trophoblast (IT) at the implantation site but with variability in staining. HPL and SP1 appeared later than HCG in ST, and the intensity of staining increased rapidly to strongly positive by wk 8. They remained strong until full term. IT stained strongly positive with HPL throughout pregnancy, and some were different from the HCG positive ones. ST were constantly negative for PAPP-A throughout pregnancy. The latter, however, was definitely seen in the cytoplasm of cytotrophoblast (CT) of early blastocyst, the superficial epithelium of the endometrium adjacent to the implantation site, in many decidual cells around the implantation site and in the amniotic membrane epithelium.

Amnion↗
PubMed1988

Inflammatory cells and the epithelium. Mast cell/nerve interactions in the lung in vitro and in vivo.

A hypothesis is presented that mast cells in and below the epithelium of the respiratory tract show functional association with nerves to form a homeostatic regulatory unit. During inflammation, mast cells may arise in situ as well as by infiltration because epithelium contains both mast cell precursors and produces factors that support their growth in vitro. Structural studies show that mast cells associate with nerves in the lung. Using a tissue culture model, we showed that sympathetic nerves formed lasting contacts with rat basophilic leukemia (RBL) cells. Electrophysiologic studies showed that nerve contact increases RBL membrane conductance, which can be mimicked by exogenous substance P (SP). Experiments with sensitized rat tracheal mucosa in Ussing chambers showed functional evidence of interaction of mast cells with SP-containing nerves: changes in short circuit current caused by antigen were blocked by the mast cell stabilizer doxantrazole and reduced by 50% by neonatal pretreatment with capsaicin. Experiments in vivo showed that lung clearance of the aerosol probe 99mTc-DTPA was increased by antigen challenge in sensitized rats. This was blocked by neonatal capsaicin treatment, again implicating SP-containing nerves. Therefore, we conclude that the functional association of mast cells with nerves is an important mechanism in regulating the local epithelial environment.

Animals↗
PubMed1987

Neuropeptides and immunity.

Our studies have clearly shown that neuropeptides have a profound effect on immunoglobulin synthesis both in vivo and in vitro. The effects varied according to the neuropeptide added or the tissue from which the lymphocytes were obtained. Substance P caused the most pronounced enhancement of both functions, especially in Peyer's patch cells, where it selectively increased IgA synthesis. Somatostatin was inhibitory, and the effect of vasoactive intestinal peptide varied according to the source of the cells. We have previously shown that neuropeptides also cause mast cell secretion and that only substance P was effective in this regard on intestinal mucosal mast cells. Therefore, we looked for microanatomic relationships between peptidergic nerves and immune effector cells. Mast cells appear to have structural associations with neuropeptides-containing nerves in the intestine. Nerve growth factor, known to promote the growth of sensory afferent and sympathetic nerves, has significant direct effects on mast cells. In vitro, this substance caused enhanced antigen mediated histamine release and, in vivo, extensive mast cell hyperplasia. Also, in humans, we were able to produce increased numbers of mast cell/basophil colonies from peripheral blood in the presence of nerve growth factor.

Animals↗
PubMed1987

Mast cell involvement in various inflammatory processes.

Mast cells from different tissue sites may have different histochemical, chemical, and functional properties. Whatever the basis for these differences, they must be important in terms of their biologic significance. Through their mediators, mast cells are involved in many different acute and chronic inflammatory processes. They act in delayed hypersensitivity, immediate hypersensitivity, and in granulomatous reactions. They can influence phagocytosis, chemokinesis, and many aspects of immune activity in several different T and B cell pathways, to mention only a few effects. Mast cells are involved in repair processes including fibroblast function and fibrosis. Their growth may be influenced by T cell-derived factors as well as factors derived from the epithelium. They appear to be intimately involved with nerves and can form apparent communications with neurones, especially those containing Substance P, which causes all types of mast cells to degranulate. Mast cells may therefore act as central switchboards between the central nervous system and migrating and sessile cell types in inflammatory processes.

Animals↗
PubMedDate not supplied

Chordoma: cytologic and immunocytochemical study of four cases.

We present the cytologic features and the immunocytochemical profile of four cases of chordoma on fine-needle aspiration biopsies. The physaliferous cells in signet-ring, pearl-like formations and the trabecular arrangement with rounded contours are distinctive. Other cell types and cellular arrangements are also described. The negative immunoreactivity of carcinoembryonic antigen (CEA) and the positive staining pattern for neuron-specific enolase (NSE), S-100 protein, epithelial membrane antigen (EMA), and keratin provide a profile that, in the appropriate clinical setting, can be useful in the differential diagnosis of chordoma from similar-appearing neoplasms in small biopsies and fine-needle aspirates.

Adult↗