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S C Bell

Publications and source records attributed to S C Bell.

At least 109 records · Page 6Linked to original sources
PubMed1993

Immunohistochemical expression of tumour-associated glycoprotein and polymorphic epithelial mucin in the human endometrium during the menstrual cycle.

An epitope defined by a second generation murine monoclonal antibody (LU-BCRU-G7) produced against a breast tumour-associated fucosylated glycoprotein of M(r) 230,000 was found to exhibit phase specific reactivity in human endometrium during the menstrual cycle. Distribution and cycle related expression of the LU-BCRU-G7 determinant was different from the staining patterns observed with antibodies that react with the polymorphic epithelial mucins, HMFG 1 and NCRC 11, as determined by immunohistochemistry. Initial expression of the LU-BCRU-G7 determinant was associated with the peri-basal region of glandular epithelial cells with maximal staining during the mid-secretory phase. Diffuse cytoplasmic staining was also observed from day 10 to day 26, with a marked increase in the early secretory phase. Reactivity of NCRC 11 also showed maximal expression in the midsecretory phase with no reactivity detected in early and mid-proliferative phases. The HMFG 1 defined epitope exhibited the opposite pattern of expression with maximal reactivity in the proliferative phase and little or no reactivity in the secretory phase. These findings suggest that expression of the LU-BCRU-G7, HMFG 1 and NCRC 11 defined determinants in the human glandular epithelium of the endometrium is differentially hormonally regulated, and may be of value as markers for endometrial function.

Antigens, Neoplasm↗
PubMed1992

Immune responses in common and grey seals during the seal epizootic.

Serological surveys of common and grey seals were performed to monitor the spread of the phocid distemper outbreak in 1988 and its effects on the host immune response. The disease affected mainly common seals; grey seals were largely unaffected but did have anti-CDV antibodies which developed during 1988. Canadian seals, both common and grey, showed evidence of a morbillivirus infection but without the apparent mortality observed in British common seals. Common seal circulating immunoglobulin levels were not greatly affected during the outbreak, although there was some reduction in the most severely affected pups. Vaccination of common seals with CDV antigens elicited high titres of antibodies and produced clinical protection. Vertical transmission of host immunity was shown in grey seals although the longevity of protection has not been determined. The large population of common seals which are not immune emphasises that such an epizootic could have serious consequences again in the future.

Animals↗
PubMed1992

Immunohistochemical expression of endometrial proteins and pregnancy outcome in frozen embryo replacement cycles.

The expression of two endometrial proteins, pregnancy-associated endometrial alpha-2 globulin (alpha-2 PEG) and 24K protein, was examined immunohistochemically in an attempt to identify a marker or a pattern which would predict subsequent implantation. Patients who had undergone in-vitro fertilization cycles and had at least three frozen embryos were recruited into the study. They received two cycles of hormone replacement therapy. The first was a monitored cycle in which dated endometrial biopsies were taken for immunohistochemical assessment using monoclonal antibodies to alpha-2 PEG and 24K protein and also for standard histological dating. In the second cycle, the frozen-thawed embryos were replaced. The results of the monitored cycle were then correlated with the pregnancy outcome in the transfer cycle. Ten patients conceived, of whom eight had a pattern of low immunohistochemical staining of alpha-2 PEG and high immunohistochemical staining of 24K. In the 15 patients who did not conceive, four had the same endometrial protein pattern (P less than 0.05). In the 13 specimens classified as histologically in phase, 10 (71%) showed incompatible protein expression. We conclude that the pattern of expression of the endometrial proteins alpha-2 PEG and 24 K may be potentially useful to indicate a receptive endometrium. Immunohistochemistry may yield information on endometrial development which is not apparent from routine histological assessment.

Antibodies, Monoclonal↗
PubMed1991

Production of insulin-like growth factor-binding proteins by human central nervous system tumors.

Central nervous system (CNS) tumor cells possess specific receptors for insulin-like growth factors (IGFs) and respond to the growth-promoting effects of IGFs in cell culture. In the present study, we asked whether CNS tumors also produce IGF-binding proteins (BPs) which may modulate the effects of IGFs on CNS tumor cells. Primary cell cultures were established from 20 CNS tumors. Dot blot analysis with 125I-labeled recombinant human IGF-I revealed IGF-binding activity in serum-free conditioned medium from 5 of 7 meningiomas, 7 of 8 malignant gliomas, and 3 of 5 other CNS tumors. Specific IGF BPs in conditioned medium were characterized further by Western ligand and immunoblotting, affinity labeling, and precipitation with specific antibodies against human IGFBP-1, -2, and -3. All conditioned media tested contained an Mr 35,000 BP which was recognized by antiserum against IGFBP-2 and an Mr 24,000 BP that was not recognized by available antisera. Medium conditioned by meningiomas (and one glioma) also contained Mr 45,000 and 50,000 IGF BPs, similar in size and/or immunological properties to growth hormone-dependent BPs present in normal human serum (IGFBP-3). Ligand blotting also showed that meningiomas produce an Mr 29,000 BP; immunoblotting and immunoprecipitation of affinity-labeled IGF-BP complexes confirmed that this BP is recognized by antiserum against IGFBP-1. Immunohistochemistry with specific monoclonal antibodies demonstrated that IGFBP-1 is abundant in pathological specimens of meningiomas and that lower amounts also are detected in malignant gliomas. We conclude that human CNS tumor cells produce a variety of IGF BPs in cell culture, including several that are similar in size and immunological properties to previously characterized human IGF BPs. Immunohistochemistry with specific monoclonal antibodies against IGFBP-1 confirms that this BP is present in vivo, further supporting the concept that IGF BPs may contribute to the regulation of growth in human CNS tumors.

Blotting, Western↗
PubMed1991

Multiple forms of mRNA encoding human pregnancy-associated endometrial alpha 2-globulin, a beta-lactoglobulin homologue.

Human pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) is the major secretory protein product of the endometrium during embryo implantation and the first few weeks of pregnancy. It is a homologue of beta-lactoglobulin, a retinol binding protein, but unlike beta-lactoglobulin it is not found in the mammary gland. The cloning and sequencing of 34 alpha 2-PEG clones has revealed several minor variant forms indicative of alternatively spliced alpha 2-PEG pre-mRNA. These minor forms have also been detected amongst uncloned cDNA after PCR amplification. Some of these mRNAs would give rise to forms of alpha 2-PEG protein lacking internal sequences, whereas others affect the mRNA sequences on the 3' boundary of the presumed termination codon. Sequences within the cDNA clones are consistent with the existence of splice sites, and together with similarities found between alpha 2-PEG cDNA and beta-lactoglobulin gene sequences there is good evidence in support of an unusual scheme for the alternative splicing of alpha 2-PEG pre-mRNA involving both alternative 5' splice sites and alternative 3' splice sites. This scheme suggests that the alpha 2-PEG and beta-lactoglobulin genes share a similar structure in at least two regions, and it is likely that beta-lactoglobulin pre-mRNA would show a similar pattern of alternative splicing for one of these regions.

Amino Acid Sequence↗
PubMed1991

Canine distemper viral antigens and antibodies in dogs with rheumatoid arthritis.

Dogs with canine rheumatoid arthritis had significantly elevated levels of antibodies to canine distemper virus. This increase was particularly seen in the synovial fluids, compared with paired sera, and was not found in dogs with infective arthropathies, osteoarthritis or in osteoarthritis secondary to rupture of the cranial cruciate ligament. Analysis of the immune complexes precipitated from synovial fluids showed immunoglobulins in all types of arthropathy. Western blotting analyses showed reactivity with anti-distemper antisera in immune complexes from dogs with rheumatoid arthritis, but not in immune complexes from dogs with other joint diseases. These results suggest that there are increased immune responses to distemper in canine arthritis and that these may be due to the presence of this paramyxovirus in affected joints. The implications for the role of a possible infectious agent in rheumatoid arthritis in the dog are considerable.

Animals↗
PubMed1991

Protein kinase C independent restoration of specific immune responsiveness in common variable immunodeficiency.

7,8-Disubstituted guanine ribonucleosides represent a class of B lymphocyte agonists that utilize a protein kinase C-independent signaling pathway. These compounds provide an alternate T helper signal for B cells and enhance antigen-specific humoral responses in the murine model and in an IL-2-dependent human model in vitro. They effectively restore high level immune responses in a variety of murine models of immunodeficiency both in vivo and in vitro. In this study we examined the potential of these compounds to improve antibody responses generated by cultured cells from patients with common variable immunodeficiency (CVI). The inability to mount normal humoral responses to antigen was confirmed in nine patients with diagnosed CVI (CVI: 37 +/- 16, normal 653 +/- 116 plaque-forming cells (PFC)/culture; P less than 0.001). In cultured lymphocytes from eight of the nine patients studied, a normal level or greater responses to nominal antigen could be elicited by antigen in the presence of the immunostimulatory nucleoside 7-methyl-8-oxoguanosine (7m8oGuo). The average response to antigen increased from 37 +/- 16 without nucleoside to 1733 +/- 488 PFC/culture in its presence (P less than 0.002). Restoration of specific immune responses was an antigen-dependent and nucleoside dose-dependent event. Signaling by 7m8oGuo rendered the response to antigen protein kinase C independent in cultures of cells from normal donors as well as from CVI patients. These data substantiate (i) that a non-C-kinase signaling pathway for antigen-dependent differentiation exists, (ii) that this pathway can function normally in B cells from patients with CVI when triggered appropriately, and (iii) that 7,8-disubstituted guanine ribonucleosides can convert a C-kinase-dependent signaling event to a C-kinase-independent signaling event. Substituted guanine ribonucleosides may have potential as immunotherapeutic agents for patients with CVI.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Effect of clomiphene citrate on the synthesis and release of the human beta-lactoglobulin homologue, pregnancy associated endometrial alpha 2-globulin, by the uterine endometrium.

As an extension to a previous study to examine the effects of clomiphene citrate (CC) on human chorionic gonadotrophin/luteinizing hormone (LH) receptors in human corpora lutea, we sought to determine the effect of CC on the synthesis of the beta-lactoglobulin homologue, pregnancy associated endometrial alpha 2-globulin (alpha 2-PEG) by the luteal phase human endometrium. Seventeen normally-cycling women aged 25.9 +/- 2.1 years (mean +/- SE), undergoing elective tubal ligation, were divided into four groups consisting of controls (n = 2) and three treatment groups. Each of the treatment groups (n = 5/group) was treated with either 50 mg (group 1), 100 mg (group 2) or 150 mg (group 3) of CC daily on days 5 to 9 of the cycle. Portions of endometrial tissue were obtained by curettage 7 to 9 days following the urinary LH surge and were either fixed for histological analyses or cultured in vitro in the presence of [35S]methionine. Tissue media (TCM) that were analysed by two-dimensional gel electrophoresis followed by fluorography indicated that the synthesis of alpha 2-PEG was most markedly reduced in groups 2 and 3. Densitometric scans of TCM Western blots and radioimmunoassay (RIA) of TCM showed that the overall synthesis of alpha 2-PEG decreased from 5.8 +/- 1.9 arbitrary units (AU) and 371.2 +/- 239.3 ng/ml in group 1 to 3.1 +/- 0.8 AU and 69.4 +/- 24.9 ng/ml, and 2.7 +/- 1.1 AU and 52.4 +/- 19.8 ng/ml in groups 2 and 3 respectively. On cycle days 20-22, control values were 5.8 AU and 498.1 ng/ml respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells.

The decidualized endometrium during the first trimester of pregnancy synthesizes and secretes a 32-kDa insulin-like growth factor-binding protein (termed hIGFBP-1) at high levels. IGFBP-1 is the major soluble protein product of this tissue and is principally localized to the differentiated endometrial stromal cell, the decidual cell. In the present study long term culture of stromal cells from the nonpregnant endometrium have been employed to elucidate the hormonal requirements for IGFBP-1 production. Immunoreactive IGFBP-1 was undetectable in control cultures. However, inclusion of medroxyprogesterone acetate (MPA) induced rates of 0.35 +/- 0.09 microgram/0.1 mg cell DNA.day (mean +/- SEM; n = 5) after 20-30 days. In these cultures cells exhibited morphological changes consistent with decidual cell differentiation. In all cultures removal of MPA after exposure for 10-16 days, with or without subsequent inclusion of relaxin (RLX), increased production of IGFBP-1 450- to 4600-fold to rates of 150-710 micrograms/0.1 mg cell DNA.day or 26-131 micrograms/10(6) cells.day on days 24-26. The rates tended to be higher with the inclusion of RLX and were sustained in contrast to cultures without RLX, where rates fell by day 30. Individual cultures responded differently to RLX when added from the initiation of culture, with either a response similar to MPA alone or a cyclical change in production, achieving maximal rates of 190-290 micrograms/0.1 mg cell DNA.day. Cultures in which RLX alone induced high IGFBP-1 high production were obtained from endometrium during the progesterone-dominated luteal phase. In cultures exhibiting high rates of immunoreactive IGFBP-1 production, the protein represented their major secretory protein product. This was confirmed by [35S]methionine incorporation and the presence of IGFBP-1 as the predominant protein in serum-free culture medium. The immunoreactive IGFBP-1 isolated from culture medium was found to be identical, by a number of criteria, with IGFBP-1 derived from decidual tissue. These results were consistent with a primary role of progestin exposure, whether in vivo or in vitro, in converting endometrial stromal cells to cells potentially able to exhibit the high rates of IGFBP-1 production typical of the decidualized endometrium of pregnancy.

Adult↗
PubMed1990

6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents.

A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely potent and selective inhibitor of canine PDE fraction III and a long-acting, potent, orally active inotropic vasodilator agent in various canine models. Additional benzoxazin-6-yl and -8-yl compounds were also prepared. Altering the pyridazinone substitution from the 6-position to the 7-position produced a 14-fold increase in the iv cardiotonic potency (ED50) from 77 to 5.4 micrograms/kg while substitution at the 8-position reduced potency. Methyl substitution at various sites in the molecule was also examined. Positive inotropic activity was maintained for between 8 and 24 h after a single oral dose (100 micrograms/kg) of bemoradan in dogs, thus making it one of the most potent and long-acting orally effective inotropes yet described. Bemoradan is currently under development as a cardiotonic agent for use in the management of congestive heart failure.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Assessment of endometrial differentiation and function.

The failure to produce an endometrium which is receptive and able to support implantation may underlie some cases of infertility and represent a contributory factor preventing higher pregnancy rates in IVF. This is of direct relevance to ovarian hyperstimulation protocols which may affect the pattern of endometrial differentiation and function and to patients possessing intrinsic defects in their endometrial response. It is apparent that markers of endometrial differentiation are required, particularly those defining the ability of the tissue to support implantation. The common method of assessing endometrial differentiation by histological evaluation, which has been substantially improved by techniques of morphometric analysis, depend upon alterations in endometrial structure. However, the production of monoclonal antibodies to proteins and epitope-bearing mucins which exhibit specific patterns of expression during the luteal phase now also enables immunohistological assessment of endometrial differentiation. Whether these proteins mediate essential functions is not known but as they represent end-points of hormone action this would suggest that their measurement may form the basis of tests of endometrial function and supplement morphometric analyses.

Embryo Implantation↗
PubMed1990

Immunohistological distribution of the secretory endometrial protein, 'pregnancy-associated endometrial alpha 2-globulin', a glycosylated beta-lactoglobulin homologue, in the human fetus and adult employing monoclonal antibodies.

We have previously demonstrated that pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the human glycosylated beta-lactoglobulin homologue (HG-BLG), is quantitatively the major secretory soluble protein product of the secretory endometrium during the latter half of the menstrual cycle and decidua spongiosa of the gestational endometrium during early pregnancy, and is principally localized to the glandular epithelium. In the present study employing monoclonal antibodies in immunohistological techniques, the distribution and localization has been examined in normal and pathological tissues of the adult and first-trimester fetus. No significant staining for alpha 2-PEG was detected in any non-reproduction-associated tissue in the normal adult nor any tissue in the fetus. In the adult, most intense staining was associated with the endometrial glandular epithelium in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle and pregnancy, appearance of alpha 2-PEG in endometriosis was strongly linked with its appearance in uterine endometrial tissue, suggesting that endometriotic tissue exhibited competence to respond to the same hormonal milieu required to induce synthesis in the uterine endometrium. Localization to the mucosal epithelium of the Fallopian tube was consistent with synthesis of alpha 2-PEG, albeit at low levels, and staining at this site reflected fluctuations of staining within the uterus. Of the pathological specimens examined, staining was only detected in a proportion of ovarian carcinomas. No staining was detected in the mammary gland, a site of beta-lactoglobulin synthesis, whether obtained during pregnancy or lactation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1990

Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated beta-lactoglobulin homologue, in successful and unsuccessful assisted conception.

Pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) is the major secretory protein of the endometrium in the late luteal phase. Serum levels were measured during the implantation period in successful and unsuccessful cycles of assisted conception. The effects of two different treatment regimens were also compared. All patients who underwent ovulation induction therapy showed an endometrial response as measured by a rise in serum levels of alpha 2-PEG. This rise was the same regardless of either implantation or the method of ovulation induction used. Higher levels were seen at oocyte recovery in those cycles treated with clomiphene citrate and may reflect a disordered endometrial response involving a direct effect of the drug on the endometrium. This may explain the difference in success rates in assisted conception when an alternative treatment initially involving down-regulation of endogenous gonadotrophin activity and subsequent administration of gonadotrophins is used. The rise in serum levels seen in pregnancy did not differ statistically according to whether the pregnancy progressed normally or subsequently aborted. Considerably reduced alpha 2-PEG production by the endometrium was identified in one patient who subsequently aborted. The measurement of serum levels of alpha 2-PEG during the implantation phase is unlikely to provide a clinical tool either for early detection of pregnancy or as a prognostic factor of successful implantation.

Abortion, Spontaneous↗
PubMed1990

Immunohistological distribution of the secretory endometrial protein, 'pregnancy-associated endometrial alpha 2-globulin', a glycosylated beta-lactoglobulin homologue, in the human fetus and adult employing monoclonal antibodies.

We have previously demonstrated that pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the human glycosylated beta-lactoglobulin homologue (HG-BLG), is quantitatively the major secretory soluble protein product of the secretory endometrium during the latter half of the menstrual cycle and decidua spongiosa of the gestational endometrium during early pregnancy, and is principally localized to the glandular epithelium. In the present study employing monoclonal antibodies in immunohistological techniques, the distribution and localization has been examined in normal and pathological tissues of the adult and first-trimester fetus. No significant staining for alpha 2-PEG was detected in any nonreproduction-associated tissue in the normal adult nor any tissue in the fetus. In the adult, most intense staining was associated with the endometrial glandular epithelium in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle and pregnancy, appearance of alpha 2-PEG in endometriosis was strongly linked with its appearance in uterine endometrial tissue, suggesting that endometriotic tissue exhibited competence to respond to the same hormonal milieu required to induce synthesis in the uterine endometrium. Localization to the mucosal epithelium of the Fallopian tube was consistent with synthesis of alpha 2-PEG, albeit at low levels, and staining at this site reflected fluctuations of staining within the uterus. Of the pathological specimens examined, staining was only detected in a proportion of ovarian carcinomas. No staining was detected in the mammary gland, a site of beta-lactoglobulin synthesis, whether obtained during pregnancy or lactation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1990

Binding proteins for insulin-like growth factors in the human ovary: identification, follicular fluid levels and immunohistological localization of the 29-32 kd type 1 binding protein, IGF-bp1.

The occurrence of pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 29-32 kd insulin-like growth factor binding protein, now termed type 1 or IGF-bp1, has been examined in the human ovary by monoclonal and polyclonal antibody based radioimmunoassay and immunohistological techniques. Follicular fluids aspirated from 51 follicles of 32 women undergoing hyperstimulation involving buserelin or clomiphene-based protocols contained 35.5-276.0 ng/ml (mean 101.0 mg/ml) of immunoreactive IGF-bp1. Mean fluid concentrations were three times the level of IGF-bp1 detected in paired serum samples, available for 21 women. Immunoreactive IGF-bp1 in follicular fluid exhibited similar dose-response curves to purified protein and amniotic fluid and immunoreactive IGF-bp1 coeluted in gel filtration with a peak of [125I]-IGF-1 binding corresponding to the elution profile of purified IGF-bp1. Gel filtration also revealed the presence in follicular fluid of a greater than 100 kd binding protein with a binding capacity equal to IGF-bp1 under the conditions employed. A highly significant correlation (P less than 0.001) was found between follicular fluid progesterone and IGF-bp1 and a correlation of lower significance was found between oestradiol and IGF-bp1 (P less than 0.05). However, only low levels of immunoreactive IGF-bp1 were detected in supernatant media of granulosa cells in culture (range undetectable to 2.3 ng/ml). Employing monoclonal antibody-based immunohistology, immunoreactive IGF-bp1 was consistently associated with luteinized granulosa cells of corpora lutea rather than paraluteal cells and its intensity of reactivity appeared to reflect luteal phase steroid hormone profiles. No consistent reactivity was detected in preovulatory follicles and granulosa cells in culture, although reactivity was associated with primordial oocytes. Immunoreactive IGF-bp1 was detected in six of nine supernatant media of explants of luteal tissue obtained from five corpora lutea, with levels ranging from undetectable to greater than 200 ng/ml. These observations suggest that IGF-bp1 is primarily related to luteinization of the granulosa and the resultant luteal cells, and if produced by the luteal cells, additional exogenous factors are required to induce production by granulosa cells in vitro.

Adult↗
PubMed1990

Human 'pregnancy-associated endometrial alpha 1-globulin', a 32 kDa insulin-like growth factor-binding protein: immunohistological distribution and localization in the adult and fetus.

We have previously shown that pregnancy-associated alpha 1-globulin, a small molecular weight (32 kDa) insulin-like growth factor-binding protein (IGF-BP), is quantitatively the major secretory protein product of the decidualized endometrium during human pregnancy and is localized principally in the decidual cell. In the present study, employing monoclonal antibodies in immunohistological techniques, the distribution and localization of IGF-BP has been examined in normal and pathological tissues of the adult and first trimester fetus. In the adult, most intense reactivity was associated with endometrial stroma and their derived decidual cells in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle, the appearance of IGF-BP in endometriotic tissue was linked with its appearance in uterine endometrial tissue. The only other adult cells where significant staining was detected was in the luteal cells of the corpus luteum. Production of the protein was not a feature of carcinomas. In the fetus, the protein was localized in lymphoid-myeloid progenitor cells and hepatocytes of the liver and at lower levels in testicular Leydig cells and adenocortical cells. These observations suggest highly specific tissue expression of this protein and support a specialized role for this protein in progenitor cells of the lymphomyeloid system, in certain steroid hormone-producing cells and in the decidual cell in pregnancy.

Endometrium↗