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Biomedical subjects

E Mann

Publications and source records attributed to E Mann.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells.

The c-erbB-2 gene encodes a M(r) 185,000 tyrosine kinase receptor (p185) with extensive homology to the epidermal growth factor receptor. We have conducted mechanistic studies with several anti-p185 monoclonal antibodies (TAb 250, -255, -257, -260, and -263) directed against the extracellular domain of p185 utilizing the SKBR-3, BT-474, and SKOV-3 cancer cell lines. Several of these antibodies exhibited ligand-mimicking properties: they induced tyrosine phosphorylation of p185; increased the catalytic activity of the receptor substrate phospholipase C-gamma 1; exhibited time- and pH-dependent internalization; induced receptor down-regulation; and increased the turnover of the p185 protein delta 3-fold. However, there was not a universal correlation between the antibody-mediated ligand-like effects and growth inhibition. TAb 250 inhibited BT-474 cells but did not alter p185 phosphotyrosine content or increase receptor turnover in these cells. TAb 260 increased p185 protein turnover but did not affect proliferation of the SKOV-3 cell line. Furthermore, blockade of TAb 250-induced receptor phosphorylation with the tyrosine kinase inhibitor tyrphostin 50864-2 did not abrogate TAb 250-mediated growth inhibition of SKBR-3 cells. These data suggest that ligand-like effects mediated by p185 antibodies are not critical for the growth inhibition of c-erbB-2-overexpressing carcinoma cells.

Adenocarcinoma↗
PubMed1994

Cervical carcinoma in the Grampian region (1980-1991): a population-based study of survival and cervical cytology history.

OBJECTIVES: To study survival in women treated for cervical carcinoma in Grampian region, to identify clinical and pathological prognostic factors, and to correlate survival with cytology history. DESIGN: A retrospective study of all cases of cervical carcinoma using a prospectively gathered database. Data validated by 1 in 10 randomised retrospective case note sampling. SETTING: Aberdeen Royal Infirmary. SUBJECTS: Three hundred and sixty-three women resident within Grampian diagnosed as having cervical carcinoma between 1980 and 1991, with five-year survival data on the 206 diagnosed by the end of 1986. MAIN OUTCOME MEASURE: Five-year survival rates. RESULTS: The mean annual incidence of cervical carcinoma in our population was 11.2 per 100,000 women, with an overall five-year survival of 67% in those under 40 years of age and 60% in those aged 40 years and over. On univariate analysis, survival was significantly adversely affected by tumour stage, grade and absence of previous smears. On multivariate analysis, the effect of previous smear history was lost, but stage and grade remained strong independent risk factors for survival. There was no significant difference in five-year survival by age or tumour type. CONCLUSIONS: The prognosis of cervical carcinoma in Grampian region was independently affected only by stage of disease and tumour grading and cervical smear history.

Adult↗
PubMed1993

Identification and characterization of binding proteins for inhibin and activin in human serum and follicular fluids.

Inhibins and activins are produced by a variety of tissues and may have important endocrine and paracrine roles in development, reproduction, and hematopoiesis. However, little is known regarding the physical properties or concentrations of inhibin and activin in biological fluids. Binding proteins for inhibin or activin in serum or at production or target sites may have important implications for restricting the bioactivity of these hormones and may alter the immunoreactivity of these molecules in biological fluids. The objective of this study was to identify inhibin- and activin-binding proteins in human serum (HS) and follicular fluid (hFF) and determine the ability of these proteins to alter biological or immunological activity. In HS, [125I]activin and inhibin bound to a protein identified as alpha 2-macroglobulin (alpha 2M) using three criteria: 1) [125I]inhibin and activin bind purified alpha 2M, but not several other serum proteins tested; 2) complexes formed by [125I]inhibin and activin in HS and in the presence of purified alpha 2M elute with similar retention times on HPLC; and 3) preadsorption of HS with alpha 2M antiserum inhibits inhibin and activin binding to this protein while antiserum directed against follistatin or other serum proteins had no effect. A small amount of a lower mol wt [125I]activin-follistatin complex was also found in HS. This complex eluted with a retention time similar to that of activin bound to purified porcine follistatin. Binding of inhibin to follistatin could not be detected in HS. In contrast, follistatin was the major binding protein of both activin and inhibin in hFF. Concentrations up to 100 micrograms/ml purified alpha 2M had no effect on the bioactivity or immunoreactivity of either inhibin or activin. In contrast, follistatin inhibited both activin-stimulated pituitary FSH release and K562 hemoglobin production as well as antiserum binding in a specific activin-A immunoassay. Follistatin did not interfere with inhibin immunodetection. These data indicate that two inhibin- and activin-binding proteins are present in different relative amounts in HS and hFF, alpha 2M, the primary binding protein in HS, did not alter inhibin or activin bio- or immunoactivity under the conditions of these experiments, while follistatin, the major binding protein in hFF, may mask activin's bio- and immunoactivities.

Activins↗
PubMed1992

A population-based study of microinvasive disease of the cervix--a colposcopic and cytologic analysis.

A study of 61 cases of microinvasion of the cervix occurring in our population between 1980 and 1989 is reported. The mean age of the women was 39 years, compared with 30 years for cervical intraepithelial grade 3 (CIN III) and 47 years for frank invasion, respectively. Colposcopic suspicion of microinvasion was present in 31 cases, giving a sensitivity of colposcopic diagnosis of 50% and a specificity of 91%. In 21 cases (34%) there was no suspicion either cytologically or colposcopically of microinvasion. Colposcopy predicted microinvasion more accurately with increasing depth of invasion. In 28 women there had been previous smears within 10 years available for review. The time interval between the first abnormal smear and the histological diagnosis ranged from 1 month to 9.8 years (mean, 4 years).

Adult↗
PubMed1992

Molecular genetic analysis of two distinct receptors for mammalian bombesin-like peptides.

The mammalian bombesin-like peptides are known to be growth factors for certain cells with high-affinity bombesin receptors and have been implicated as autocrine growth factors influencing the pathogenesis and progression of a subset of human small-cell lung carcinomas. Thus, antagonists that interfere with bombesin receptor-ligand interaction might prove to be of value in treatment of gastrin-releasing peptide (GRP)-responsive tumors. A precise definition of the structure and properties of the bombesin receptors found on human lung cancer cells would provide important information for the design and rational application of such antagonists. Recently, we isolated cDNA clones encoding two distinct receptors for the mammalian bombesin-like peptides, GRP, and neuromedian B (NMB). The two receptors show 56% amino acid identity, encode seven putative transmembrane domains, and are members of the G-protein-coupled receptor superfamily. Ligand-binding studies show that while both receptors can be activated by either GRP or NMB, one receptor has a higher affinity for GRP than for NMB (GRP-R), while the other has a higher affinity for NMB than for GRP (NMB-R). A different spectrum of antagonists is needed to block responses from the two different receptors. These studies indicate that it will be critical in future studies to define which bombesin receptor subtypes are present on a given tumor to optimize the potential therapeutic benefit of antagonists in blocking growth.

Amino Acid Sequence↗
PubMed1991

Phosphorylation of alpha-crystallin B in Alexander's disease brain.

The phosphorylation of alpha-crystallin B was studied in homogenates of autopsy samples of brain tissue from patients with Alexander's disease, a condition characterized by over-expression of this protein. After incubation in the presence of [gamma-32P]ATP and cAMP the homogenates were analyzed by two-dimensional electrophoresis, (isoelectric focusing followed by SDS-PAGE). Three major polypeptides having the same molecular weight as bovine lens alpha-crystallin B and pIs 7.1, 6.9 and 6.7 were detected in the Coomassie blue stained gels. These three polypeptides were recognized by an alpha-crystallin B-specific antiserum in Western blots. The polypeptides with pIs 7.1 and 6.7 co-migrated in isoelectric focusing gels with bovine lens alpha B and its phosphorylated form alpha Bp, respectively. Radioautography of the two-dimensional gels demonstrated the presence of 32P in the most acidic polypeptide. The results demonstrate the occurrence of alpha B phosphorylation in Alexander's disease brain tissue.

Blotting, Western↗
PubMed1991

Molecular cloning of the bombesin/gastrin-releasing peptide receptor from Swiss 3T3 cells.

The mammalian bombesin-like peptides gastrin-releasing peptide (GRP) and neuromedin B regulate numerous and varied cell physiologic processes in various cell types and have also been implicated as autocrine growth factors influencing the pathogenesis and progression of human small cell lung carcinomas. We report here the molecular characterization of the bombesin/GRP receptor. Structural analysis of cDNA clones isolated from Swiss 3T3 murine embryonal fibroblasts shows that the GRP receptor is a member of the guanine nucleotide binding protein-coupled receptor superfamily with seven predicted hydrophobic transmembrane domains. In vitro transcripts from cloned cDNA templates encompassing the predicted protein coding domain, when injected into Xenopus oocytes, resulted in expression of functional GRP receptors. The predicted amino acid sequence of the open reading frame in cDNA clones matches the amino-terminal sequence as well as the sequence of four tryptic fragments isolated from the purified protein. Expression of the GRP receptor cDNA in model systems potentially provides a powerful assay for the development of subtype-specific receptor antagonists that may prove to be of therapeutic importance in human small cell lung carcinoma.

Amino Acid Sequence↗
PubMed1991

[The influence of different electrolytes on the electrochemical polarization behaviour of dental amalgams].

The measurements of electrochemical polarization of dental amalgams was studied in 5% sodium chloride aqueous solutions, in an artificial saliva and in natural saliva with different pH-values. The non-gamma-2-amalgams have been reported to have higher corrosion resistance in comparison to gamma-2-phase containing amalgams. The results show that the electrochemical corrosion behaviour is strongly differentiated using natural saliva.

Corrosion↗
PubMed1990

Purification and characterization of the bombesin/gastrin-releasing peptide receptor from Swiss 3T3 cells.

The bombesin/gastrin-releasing peptide (GRP) receptor was solubilized from Swiss mouse 3T3 cell membranes in an active form and was purified about 90,000-fold to near homogeneity by a combination of wheat germ agglutinin-agarose and ligand affinity chromatography. The purified receptor displayed a single diffuse band with a Mr of 75,000-100,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After treatment of the receptor with N-glycanase, removing N-linked oligosaccharide moieties, the protein yielded a Mr = 38,000 band. These results agree with the Mr value estimated for the GRP receptor that was labeled on Swiss 3T3 cells by cross-linking to 125I-GRP1-27. GRP1-27 bound to the purified receptor with a Kd of 0.038 +/- 0.019 nM. By comparison, the soluble receptor in unfractionated extracts and intact membranes displayed a Kd for GRP1-27 of 0.036 +/- 0.003 nM and 0.13 +/- 0.04 nM, respectively. The relative potencies of a series of GRP analogs for the soluble receptor and intact membranes indicated that the extraction procedure did not significantly alter the receptor's ligand binding specificity. However coupling of the receptor to its guanyl nucleotide regulatory protein was not maintained in the soluble extract, and a G-protein did not co-purify with the receptor. Physiological concentrations of NaCl greatly inhibited the binding of some GRP analogs to the receptor, while the binding of other analogs was not affected. A domain on the GRP molecule involving Lys-13 or Arg-17 was identified which promoted binding to the GRP receptor under conditions of low ionic strength. These findings aided the development of an effective ligand affinity resin for the purification of the GRP receptor.

Animals↗
PubMed1990

The apparent molecular size of native alpha-crystallin B in non-lenticular tissues.

The apparent molecular size of the native alpha-crystallin B in cytosol preparations from rat heart, brain and retina was determined by gel permeation chromatography, detecting the protein by immunochemical assay (ELISA), using an alpha-crystallin specific antiserum. Native alpha-crystallin from cytosol preparations of rat lens cortex was used as a reference. alpha-Crystallin B present in all three cytosol preparations from non-lenticular tissues eluted in a single symmetrical peak, with the same elution volume as alpha-crystallin from lens cortex cytosol preparations, corresponding to an apparent average molecular size of 0.8 x 10(6) Da. No other species could be detected. The results indicate that the alpha-crystallin aggregates characterized by an apparent average molecular mass of 0.8 x 10(6) Da, and considered to be the native, physiological form of the protein in the lens, are indeed not specific to lens tissue. Furthermore, the size of these alpha-crystallin aggregates is independent of their polypeptide composition. Aggregates found in the lens, composed of alpha A and alpha B polypeptides and their respective phosphorylated forms alpha Ap and alpha Bp, are similar in size to those found in heart, brain and retina, containing the alpha B but not the alpha A polypeptide.

Animals↗
PubMed1988

[Intracerebral hematoma from a large aneurysm of the middle cerebral artery in infancy].

The article reports on a large aneurysm of the tunica media vasorum with intracerebral haematoma in an infant of the age of 4 1/2 weeks and on the successful treatment by removal of the haematoma and extirpation of the aneurysm. The rare space-occupying lesion of the central organ seemed to point first of all to a peripheral disease due to the very unusual and highly special course in the infant; a gastrointestinal disorder seemed to be responsible for this phenomenon. It was only after observing mild convulsive manifestations that sonography was employed as a diagnostic tool, and thus the central disturbance was identified and its localisation and genesis demonstrated via computed tomography and angiographic diagnosis. Attention is drawn to the outstanding "search method" of noninvasive sonography via the still open fontanelle of the infant. This method should be employed if there is even the slightest suspicion of cerebral disease. A study of the literature shows clearly the superiority of the modern methods such as computed tomography and digital subtraction angiography over a femoralis catheter. The literature includes in particular two cases that occurred in the sixties of the present century and were comparable with that of our infant; at that time, the authors of those publications did not yet command over our present-day methods.

Cerebral Angiography↗
PubMed1987

New female perceptions of parental power.

In a study of family roles, 85 adolescent sons and daughters from 27 families initially attributed "power" roles to fathers and "support" roles to mothers. Three years later, daughters perceived power and support roles as shared, while sons still perceived the earlier dichotomy.

Adolescent↗