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Biomedical subjects

J Ellis

Publications and source records attributed to J Ellis.

At least 289 records · Page 16Linked to original sources

Toxic and genotoxic action of electric-arc welding fumes on cultured mammalian cells.

Welding fumes generated by manual metal arc welding (MMAW) with an automatic welding machine were extracted with water and both the soluble and insoluble fractions were investigated for mitotic delay and for sister chromatid exchange (SCE) induction in cultured Chinese hamster lung (Don) cells. Five flux-coated electrodes of varying composition were chosen as representative of those available. In general, water-soluble and water-insoluble fractions induced SCE in proportion to their chromium(VI) content, and any contribution from chromium(III), fluorides, nickel, manganese or other fume constituents was minor. However, mitotic delay could not be explained in terms of the chromium(VI) concentration alone. This indicated that other components of both the soluble and insoluble fractions of the fumes were capable of inducing mitotic delay. The activity of insoluble fume fractions, either in mitotic delay- or in SCE-induction, was markedly less than that of soluble fractions. This was presumably because of the lower, though still significant, bioavailability of 'insoluble' components of the fume particles.

Air Pollutants, Occupational↗

Cloned helper T cell for IgE: characterization of T cells cloned from an atopic donor with a high serum IgE.

T cells cloned from nonatopic and atopic donors were examined for the ability to help IgE production in vitro. Experiments with clones from nonatopic donors were unsuccessful in spite of isolation of four clones that promoted IgM and IgG when these were mixed with B cells from nonatopic donors and pokeweed mitogen. We reasoned that T cells regulating IgE might be found with greater frequency in atopic donors with very high serum IgE. Two T cell clones from an atopic donor with a serum IgE of 3000 IU/ml were found to drive atopic B cells to produce up to 10,000 pg/ml of IgE in vitro. This promotion of IgE secretion occurred in the absence of mitogen stimulus and appeared to decrease with higher ratios of T cells:B cells. One of the clones (A-H4) also promoted the production of IgM and IgG in addition to the IgE; however, when this clone was carried in culture for several months, this activity for IgM and IgG fell markedly, whereas help for IgE decreased less. We have speculated that these two T cell clones, with unusual activation properties, may be representative of a subset of atopic T cells responsible for maintaining the circulating B cells that spontaneously secrete IgE in vitro in patients with high serum IgE.

B-Lymphocytes↗

A second open letter to the General Medical Council.

In an open letter to the General Medical Council this independent group, drawn from several branches of the profession, expressed the belief that undergraduate medical education was failing in two respects; first, in the extent to which it equips doctors with the capacity to think critically for themselves; and secondly, in the degree to which it inculcates a broad and sensitive outlook towards the health of both individuals and communities. A remedy for both lies, in our opinion, in the better co-ordination of the different stages of medical education. Particularly important in this context is the period immediately after graduation. We therefore welcome the attention which the General Medical Council's Education Committee is now paying to this second stage. We welcome also the view which it has expressed that it is necessary to continue a broad education into the period when the qualified doctor is assuming responsibility for patient care. In this second letter we propose and discuss six aims for this period; and changes in educational organization needed if these aims are to be fulfilled.

Clinical Clerkship↗

The beneficial effect of triamcinolone acetonide on nerve repair with autogenous grafts.

Bilateral nerve cable graft repairs were made in the sciatic nerves of Wistar rats. One group of repairs was treated locally with triamcinolone acetonide (0.5 mg), one group was exposed to the systemic effects of the drug, and one group was left untreated. Nerve regeneration was measured by nerve-stimulated muscle twitch strength, as well as several electrophysiologic parameters of the compound action potential conducted through the graft. Results suggest that nerve regeneration through an autogenous graft is significantly improved by local treatment with triamcinolone acetonide. Further studies are indicated to determine appropriate dosage necessary to maximize the beneficial local effects.

Action Potentials↗

Evaluation of NH2-terminus gastrins in gastrinoma syndrome.

Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.

Chromatography, Gel↗

Identification of myoepithelial cells in human and rat breasts by anti-common acute lymphoblastic leukemia antigen antibody A12.

An immunohistological study in the human breast and the rodent breast (from inbred Ludwig/Wistar/Olac rats) was conducted with the use of a murine monoclonal antibody, which reacts with the common acute lymphoblastic antigen, a glycosylated polypeptide of a molecular weight of 100,000. The epitope, as recognized by this antibody, is expressed on myoepithelial cells of the normal human and rat breasts and was studied in the developing rodent mammary gland. Ultrastructural studies in the normal human breast clearly demonstrated the presence of the antigen on the lateral membrane of the myoepithelial cells with no staining of luminal cells, blood vessels, or stromal elements. The antigen survived prolonged enzymatic digestion of human breast tissue and could be demonstrated on myoepithelial cells in single-cell suspensions of human breast where it stained approximately 3-14% of the total cell population. The presence of this antigen on myoepithelial cells is discussed in the context of myoepithelial differentiation in the breast and the potential utility of the antibodies for cell separation.

Animals↗

Quaternary forms of classical muscarinic antagonists distinguish subpopulations of muscarinic receptors: correlation with gallamine-defined subpopulations.

Atropine and scopolamine inhibit the binding of [3H] quinuclidinyl benzilate (QNB) to muscarinic receptors of rat forebrain in a manner that suggests homogeneity of the binding sites. Under the same conditions, the inhibition by N-methylatropine (NMA) and N-methylscopolamine (NMS) of the binding of [3H]QNB is consistent with the presence of subpopulations of receptors that differ greatly in affinities toward these quaternary ligands. The subpopulations that are defined according to the affinities of NMA and NMS correlate very well with those that are defined by the use of gallamine. It is suggested that the heterogeneity in the binding of NMS explains some of the anomalous interactions between NMS and gallamine that have been reported previously.

Allosteric Site↗

Epithelial cells of the normal human breast.

A comparison has been made of the effects of different fixation protocols upon the ultrastructure of normal human breast. Pale (B) and dark (A) epithelial cells as described by previous authors are present in tissue fixed with hyperosmotic Karnovsky-type fixatives, but not where the primary fixative is isosmotic glutaraldehyde. The observed subpopulations of pale and dark epithelial cells have been directly compared with sub-groups of epithelial cells recognized by the monoclonal antibody LICR-LON-M8. The pale and dark cells bear no relation to the subpopulations of epithelial cells depicted by LICR-LON-M8.

Antibodies, Monoclonal↗

Mutagenicity of metal ions in bacteria.

The mutagenicity of 24 metal salts was investigated in plate incorporation and fluctuation assays with Salmonella TA strains or Escherichia coli WP2 uvrA pKm 101. Chromate(VI) and selenate(VI) ions were found to be mutagenic in plate incorporation assays employing conventional media. On the other hand, cadmium(II), beryllium(II), chromate(VI), and metavanadate(V) ions were detected in conventional fluctuation assays, indicating the importance of this technique in detection of metal mutagens. Modified culture media, with trimetaphosphate ions in place of orthophosphate as the sole phosphate source for bacterial growth, were also used in this study. The media modifications prevented precipitation of metals such as nickel and cadmium as their insoluble phosphates, and allowed detection of the mutagenicity of metavanadate ions in plate incorporation assays. However, the fluctuation technique using standard media was shown to detect a wider range of mutagenic metal ions than tests with modified media. It is notable that metaarsenite(III), arsenate(V), and nickel(II) ions were not found to be mutagenic in any of the assays although they are known to be carcinogenic and are mutagenic in other test systems. Their lack of mutagenicity in the modified media indicates that precipitation of these ions as orthophosphates is not the reason for their lack of activity in standard bacterial assays.

Beryllium↗

Alpha 2-adrenergic receptor-mediated regulation of adenylate cyclase in the intact human platelet. Evidence for a receptor reserve.

The alpha 2-adrenergic receptor on the human platelet is known to mediate the inhibition of adenylate cyclase activity. A comparison of the binding and response properties of intact cells revealed that the full agonists norepinephrine and epinephrine inhibit cyclic AMP accumulation with apparently higher affinity than they exhibit in inhibiting the binding of [3H]yohimbine. Additionally, Hill coefficients of the occupancy curves of the agonists were less than unity, suggesting the presence of a heterogeneous receptor population in intact platelets under conditions that permit robust inhibition of cyclic AMP accumulation. The partial agonist clonidine was found to possess the same affinity in the binding assay as in the response assay. These data are consistent with the presence of a receptor reserve in this system, a suggestion that was confirmed in experiments utilizing the irreversible alpha 2 antagonist phenoxybenzamine. The IC50 (100 nM) derived from the blockade of [3H]yohimbine binding by phenoxybenzamine was significantly less than the IC50 (550 nM) for the corresponding reversal by phenoxybenzamine of the effects of norepinephrine on cyclic AMP accumulation. Further studies demonstrated a rightward shift in the dose-response curves for the inhibition by norepinephrine of cyclic AMP accumulation following pretreatment with increasing phenoxybenzamine concentration. These data consistently indicated that occupancy of approximately 10% of the alpha 2-adrenergic receptors by norepinephrine elicits a half-maximal adenylate cyclase response. The relationship of these findings to current models of receptor-effector coupling is discussed.

Adenylyl Cyclases↗

How to present a curriculum vitae.

At times, as for example when candlelight flickers on bottle and glasses, it is not unpleasant to look into a pair of warm and friendly eyes and respond to the words "Tell me about yourself." Completing a curriculum vitae (CV), however, is a less attractive proposition, especially when applying for an appointment. Even those who are fond of talking about themselves can find it difficult. Some find it embarrassing. Some, judging from the poorly presented data which frequently accompany applications even for senior posts, are unaware of the important part the CV plays in the selection process.

Education, Medical↗

Cross-species septal transplants: recovery of choline acetyltransferase activity.

Following interruption of the fornix-fimbria pathway, hippocampal choline acetyltransferase (ChAT) activity was restored gradually by cross-species cell suspension transplants of embryonic septum. The hippocampal segment closest to the implant reached 35% of normal 17 weeks after transplantation. The overall restoration of ChAT by xenogenic cell suspension had many similarities to that reported for homogenic solid and cell suspension septal grafts. The time course of the recovery of ChAT activity was different from the time course of the ingrowth of acetylcholinesterase stained fibers reported previously.

Animals↗