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I Mason

Publications and source records attributed to I Mason.

54 records · Page 3Linked to original sources
PubMed1995

Receptor binding and mitogenic properties of mouse fibroblast growth factor 3. Modulation of response by heparin.

fgf3 has been implicated in the embryonic and fetal development of the mouse and as an oncogene in murine breast cancer. We describe a procedure to purify the product of the mouse fgf3 gene and show it to be a potent mitogen for some epithelial cell lines. Using a receptor binding competition assay, Fgf3 was shown to bind with high affinity to the IIIb isoforms of Fgf receptor (FgfR) 1 and FgfR2 (ID50 = approximately 0.8 nM) and with a lower affinity to the IIIc variant of FgfR2 (ID50 = approximately 9 nM). No competition for the binding of 125I-Fgf1 was observed for FgfR1 (IIIc), FgfR3 (IIIb and IIIc), or FgfR4. Mitogenicity assays using BaF3 cells containing individual Fgf receptors showed a pattern of response in agreement with the receptor binding results. A comparison of two mammary epithelial cell lines showed a marked difference of potency and dependence upon heparin in their response to mouse Fgf3, suggesting a complex interaction between the ligand and its low and high affinity receptors.

3T3 Cells↗
PubMed1995

A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth.

BACKGROUND: The outgrowth of the vertebrate limb bud is the result of a reciprocal interaction between the mesenchyme and a specialized region of the ectoderm, the apical ectodermal ridge (AER), which overlies it. Signals emanating from the AER act to maintain the underlying mesenchyme, called the progress zone, in a highly proliferative and undifferentiated state. Removal of the AER results in the cessation of limb bud growth, thus causing limb truncation. The best candidates for this AER-derived signal are members of the fibroblast growth factor (FGF) family, in particular FGF-4, which can maintain limb bud outgrowth following removal of the AER. However, FGF-4 is only expressed after considerable outgrowth has occurred and a well-developed limb bud has formed, and then only in the posterior part of the AER. Likewise, the other FGFs studied to date are not candidates for this activity. RESULTS: We report evidence that a recently identified member of this family, FGF-8, is expressed in the ectoderm of the prospective limb territory prior to morphological outgrowth of the limb bud in both mouse and chick. Thereafter, expression is maintained throughout the AER during limb development. We have produced and purified the FGF-8 protein, and shown that it will substitute for the AER in maintaining limb bud outgrowth in mouse embryos from which the AER has been surgically removed. FGF-8 does not, however, maintain expression of the sonic hedgehog gene. CONCLUSIONS: These results indicate that FGF-8 is an AER-derived mitogen that stimulates limb bud outgrowth. Moreover, our data suggest that FGF-8 may also be an ectodermally derived mitogen that stimulates the onset of limb bud outgrowth (budding) in the absence of a morphological AER, and indicate the possible involvement of FGF-8 in the establishment of the limb field.

Amino Acid Sequence↗
PubMed1995

Fibroblast growth factor (FGF) 3 from Xenopus laevis (XFGF3) binds with high affinity to FGF receptor 2.

We demonstrate that purified fibroblast growth factor (FGF) 3 from Xenopus laevis (XFGF3) activates the mitogen-activated protein kinase pathway and induces DNA synthesis in quiescent cells. To characterize the high affinity cell surface receptors that mediate these responses, the ligand binding domains of different FGF receptors (FGFR) were expressed on COS-1 cells, and their affinity for XFGF3 was determined. Unlabeled XFGF3 efficiently competed with 125I-FGF1 for binding to the IIIb and IIIc isoforms of FGFR2, giving 50% displacement (ID50) at 0.3-0.8 nM. Higher XFGF3 concentrations were needed to displace 125I-FGF1 from FGFR3 and FGFR1 (ID50 approximately 4 and 21 nM, respectively), indicating that XFGF3 has a lower affinity for these receptors. No association of XFGF3 with FGFR4 was found using this assay. FGFR2 isoforms isolated from both mouse and Xenopus showed similar high affinity binding of XFGF3 as determined by direct binding assays (Kd values in the range of 0.2-0.6 nM). These results indicate that the binding specificity of XFGF3 is different from that of other FGFs, and identifies FGFR2 as its high affinity receptor.

Amino Acid Sequence↗
PubMed1995

Expression of ret in the chicken embryo suggests roles in regionalisation of the vagal neural tube and somites and in development of multiple neural crest and placodal lineages.

In a screen for receptor tyrosine kinase genes regionally expressed in the developing hindbrain, we cloned and characterised the chicken ret gene. Data derived from studies of congenital human disease and from disruption of murine ret have demonstrated roles for ret in development of the kidney and enteric nervous system; the latter has been most well-studied in the avian embryo. In agreement with studies of the mouse embryo, we find expression of ret in both the intermediate mesoderm and the enteric nervous system. However, we additionally detect transcripts specifically in the vagal neural tube prior to the migration of enteric crest precursors, suggesting a possible earlier function in regionalisation of the neural tube and vagal neural crest. This spatial restriction in the neural tube is modulated by retinoic acid, but is not coordinately regulated with RAR-beta which shares a common anterior limit of expression with ret in normal embryos. Widespread expression of ret in placodal and neural crest derivatives raises the possibility of other roles in the development of the peripheral nervous system. In addition, ret may function in the spatial organisation of the epithelial somite, where it might play a role in the specification of anterior dermamyotome.

Amino Acid Sequence↗
PubMed1995

Multiple roles for FGF-3 during cranial neural development in the chicken.

FGF-3 has been implicated in the development of the hindbrain and otocyst in vertebrate embryos. Since the chicken embryo offers a favourable system in which to study the development of these structures, we have isolated and characterised cDNAs for chicken Fgf-3 and determined its pattern of expression in chick embryos from stage 3 (primitive streak) to stage 25 (early organogenesis). Within the developing cranial neural tube, Fgf-3 exhibits dynamic spatial and temporal expression. During extension of the head process, RNA is detected in the midline of the developing neural plate. In neurulating embryos, transcripts are observed initially in rhombomeres 4 and 5 of the hindbrain and later, in rhombomere 6. During hindbrain development, expression is lost from these rhombomeres, but becomes restricted to rhombomere boundaries, providing an intracellular marker which distinguishes a population of cells within boundary regions. Fgf-3 expression is elevated in ventral and medial boundary regions and is greatly reduced in dorsal parts. Studies of regenerating rhombomere boundaries show that Fgf-3 expression is induced in reforming boundaries when even-numbered rhombomere tissue is grafted next to odd, but not when like is juxtaposed to like. Fgf-3 disappears from boundary regions just prior to the loss of the morphological boundaries suggesting a boundary-associated function. Other sites of expression have also been identified. At early stages of development Fgf-3 is expressed in the epiblast and mesendoderm of the primitive streak, in mesoderm lateral to the streak and in Hensen's node. In older embryos transcripts are detected in the endoderm of the pharyngeal pouches, the ectoderm of the second and third pharyngeal arches and the stomodeum. Expression was also detected in the segmental plate and in the posterior half of the three most-recently generated somites.

Amino Acid Sequence↗
PubMed1990

Murine suppressor T cell clones specific for minor histocompatibility antigens express CD4, CD8, and alpha beta T cell receptor molecules.

We have been able to establish stable, minor histocompatibility antigen-specific, non-cytolytic, MHC-class II-restricted suppressor T cell clones and lines. These suppressor T cells rearrange, transcribe, and express alpha beta T cell receptor. An unusual feature of all our clones and lines is the co-expression of CD4 and CD8 molecules on their cell surface, a characteristic which may distinguish them from conventional helper and cytolytic T cells in this system. The fact that multiple, phenotypically and functionally identical cell lines were reproducibly obtained from this system indicates that antigen-specific down-regulation of immune functions in certain circumstances is mediated by T cells that are neither conventional cytolytic nor helper T cells.

Animals↗
PubMed1988

Familial cavernous angiomas of the brain in an Hispanic family.

We found cavernous angiomas (CA) in 10 of 22 members of a large Hispanic family. The proband had seizures, and a CA was found at surgery. He and two sisters with seizures had normal angiograms, but CT or MRI showed lesions compatible with CA. Similar abnormalities were found in two cousins with seizures and 5 of 17 asymptomatic relatives studied. MRI proved to be more sensitive than CT for identifying CA. Hispanic families appear to have a predisposition for dominantly inherited CA of the brain.

Adult↗
PubMed1987

Antitumor activity via inhibition of glycosphingolipid biosynthesis.

The production by cancer cells of glycolipids, perhaps derived partly from host glycolipids, may play essential roles in malignancy, tumor growth, immunity from host immunodefense, and metastasis. The glycolipids are derived from the primary glycolipid, glucosylceramide (GlcCer), which is formed enzymatically from ceramide and uridine diphosphoglucose (UDP-glu). Injection of an inhibitor of this enzyme into mice bearing intraperitoneal Ehrlich ascites tumor cells (EATC) resulted in complete cure of about 30% of the mice and marked prolongation of life in the remainder. Almost all of the surviving mice were immune to a second inoculation of EATC. Injection of GlcCer stimulated cancer cell growth about 50% but this was largely reversed by the inhibitor. This type of inhibitor may have wide application to cancer chemotherapy.

Animals↗
PubMed1985

Expression of c-fos in parietal endoderm, amnion and differentiating F9 teratocarcinoma cells.

The expression of the cellular proto-oncogene, c-fos, in extra-embryonic tissues of the mouse was investigated using a v-fos DNA probe and an affinity-purified antiserum raised against a C-terminal synthetic peptide. At 13.5 days of development, parietal endoderm--a tissue not previously studied using these methods--was found to express c-fos RNA at a higher level than the amnion or placenta. The previously reported dramatic increase in c-fos RNA levels in extra-embryonic membranes during gestation was found to be confined to the amnion. The antipeptide serum specifically recovered proteins with Mr values of 46,000 and 39,000 from extracts of parietal endoderm and amnion cells labelled for 15 min with 35S-methionine. On sodium-dodecyl-sulphate/polyacrylamide gel electrophoresis these proteins co-migrated with proteins immunoprecipitated using serum from rats inoculated with FBJ-MuSV-transformed cells (tumour-bearing rat serum). Pulse-chasing and 32P-labelling experiments showed that the protein with an Mr of 46,000 was rapidly converted into higher-molecular-weight phosphorylated derivatives. F9 teratocarcinoma stem cells differentiated into parietal-endoderm-like cells in response to treatment with retinoic acid and dibutyryl cyclic AMP. However, this differentiation was not accompanied by any large transient increase in c-fos RNA expression.

Amnion↗
PubMedDate not supplied

Effects of ethane dimethane sulfonate on the functional structure of the adult rat testis.

In ethane dimethane sulfonate (EDS)-treated adult Sprague Dawley rats, Leydig cells (LC) were not present up to 14 days but seen at 21 days. They increased in number thereafter and reached the values of age-matching controls (i.e., 150-day-old untreated) at day 60. Mesenchymal cell number per testis also increased and reached a peak at day 21, and remained at a higher (p<.05) value than the controls at days 28-60. LC were smaller at day 21, but were larger at days 28-60 (compared to untreated 90- and 150-day-old rats) and secreted more testosterone at day 60 compared to both control groups. Testes of treated rats had greater numbers of macrophages (except at day 28) and they were smaller than those in untreated rats and 60-day EDS rats. Immunolabeling studies on 3beta-HSD, 11beta-HSD1, and LH receptor activity and androgen data agreed with morphological findings. The relationship between mesenchymal and LC numbers during LC differentiation following EDS treatment is reminiscent of this process in prepubertal testis. The presence of increased numbers of macrophages in treated testes agreed with the role of macrophages on LC differentiation. The absence of aging signs in LC of 60-day treated rats who were 150 days of age can be attributed at least in part to their newly differentiated status in older rats (i.e., equivalent to pubertal LC and not to aged LC). Larger LC observed in EDS rats at days 28-60 and their increased testosterone secretory capacity at day 60 (compared to controls) are attributed to elevated plasma LH levels and locally produced factors in EDS rats.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Computerised biofeedback games: a new method for teaching stress management and its use in irritable bowel syndrome.

OBJECTIVES: To develop and test a computer biofeedback game designed to teach deep relaxation to patients with a stress related disorder and to assess whether relaxation can improve symptomatic episodes. STUDY DESIGN AND SETTING: An open, prospective, single centre study. Department of Gastroenterology, Royal Free Hospital, London. SUBJECTS: Forty patients with irritable bowel syndrome refractory to conventional medical treatment. MAIN OUTCOME MEASURES: Development of a computer aided biofeedback apparatus directed at the gut for teaching relaxation to patients with irritable bowel syndrome. The patients' ability to complete a computer game involving biofeedback modulated by a physiological loop that related changes in stress (monitored by electrodermal activity) to animated computer graphics. The degree to which deep relaxation was achieved was measured numerically by a progressive reduction in the sensitivity level of the biofeedback loop. The success of relaxation in ameliorating physical symptoms of irritable bowel syndrome was assessed by daily diaries in which global and weighted bowel symptom scores were entered. RESULTS: A computer biofeedback game based on animated gut imagery was successfully developed. Most patients learned to achieve progressively deeper levels of relaxation after four 30 minute biofeedback sessions (mean difference in sensitivity level 2.0 (95% confidence interval 0.96 to 2.93), p < 0.001). Use of 'dosed' relaxation when bowel symptoms were troublesome was helpful in 50% of patients. It reduced the global symptom score (mean difference 0.5 (0.02 to 0.32), p < 0.04) and the bowel symptom score (mean difference 0.8 (0.04 to 1.58), p < 0.04). At long term follow up, 64% of patients who had been helped by dosed relaxation continued to use the technique, although they had had no further contact with the hospital. CONCLUSIONS: This computer biofeedback game taught deep relaxation rapidly and effectively. Half the patients with refractory irritable bowel syndrome found the technique helpful on most occasions on which it was used. Computer biofeedback games may offer a simple, inexpensive strategy for managing other stress related medical disorders.

Adult↗