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Biomedical subjects

M Ellison

Publications and source records attributed to M Ellison.

At least 37 records · Page 2Linked to original sources
PubMed1992

Content of the neurotoxins cycasin (methylazoxymethanol beta-D-glucoside) and BMAA (beta-N-methylamino-L-alanine) in cycad flour prepared by Guam Chamorros.

Exposure to cycad seed kernel is an etiologic factor for the western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC). Traditionally processed cycad flours (n = 17) obtained from Chamorro residents of Guam and the adjacent island of Rota at risk for neurodegenerative disease were extracted and analyzed by high-performance liquid chromatography for content of beta-N-methylamino-L-alanine (BMAA) and methyl-azoxymethanol beta-D-glucoside (cycasin). Cycasin (detection limit: picomole) was present in concentrations of 0.004 to 75.93 micrograms/g (mean, 12.45 +/- 5.0 micrograms/g), and levels of BMAA (detection limit: subpicomole) ranged from 0.00 to 18.39 micrograms/g (mean, 5.44 +/- 1.56 micrograms/g). On average, cycasin content was approximately 10 times higher than that of BMAA. The largest concentrations of cycasin were found in samples from villages with a high reported prevalence of ALS/PDC. Ingestion of cycad-derived food would result in estimated human exposure to milligram amounts of cycasin per day. The cytotoxic properties of cycasin merit consideration in relation to the etiology of western Pacific ALS/PDC.

Amino Acids, Diamino↗
PubMed1988

Impotence following pelvic fracture.

A group of 42 men (mean age, 26.7 years) with pelvic fractures as the result of motor vehicle accidents were evaluated for impotence 48 hours after injury. Hormone levels were normal in all patients tested. One half (21/42) of the patients had abnormal penile:brachial arterial ratios. Of this group, 13/21 had abnormal bulbocavernosus reflex (BCR): four patients were paraplegic and nine had urethral injuries. Followup of available patients to 20 months reflects persistent impotence in those who experienced vasculogenic trauma. Only 2/21 patients with normal tests (vascular, hormonal, neurologic) complain of impotence (followup at 23 months); one of these patients is in litigation.

Adolescent↗
PubMed1985

Production of beta-human chorionic gonadotrophin by human squamous carcinoma cell lines.

Eight out of 9 human squamous carcinoma cell lines ectopically secrete the beta subunit of human chorionic gonadotrophin (beta-HCG) in amounts detectable by radioimmunoassay. In contrast, both normal and SV40-transformed keratinocytes show no such evidence of beta-HCG secretion. Ectopic beta-HCG is identical in its gel exclusion and high-performance liquid chromatographic properties to placental beta-HCG and, in radioimmunoassay, yields a dilution curve parallel to that of placental beta-HCG. Dibutyryl cyclic AMP, but not sodium butyrate, stimulates beta-HCG secretion by the one human cell line examined, LICR-LON-HN-5, suggesting that ectopic production by these cells is similar to trophoblastic beta-HCG secretion, and differs from most other non-trophoblastic cell lines previously examined.

Bucladesine↗
PubMed1984

A monoclonal antibody detecting neural and neuroendocrine differentiation.

A monoclonal antibody, named LICR-LON-E36, has been produced to the acidic fraction of soluble protein extracts of human brains. Using immunocytochemistry, it stained normal peripheral nerves, adrenal medulla, pancreatic islets, and enterochromaffin cells, in addition to recognizing an intracytoplasmic epitope in phaeochromocytomas, carcinoid tumors, some small-cell anaplastic lung, and a few breast carcinomas. Microenzyme-linked immunosorbent assay and electrophoretic nitrocellulose blotting experiments confirmed that the antibody is not directed at neuron-specific enolase. Its potential use as an immunological probe for neural and neuroendocrine differentiation is discussed.

Adrenal Medulla↗
PubMed1982

Role of copper in collagen cross-linking and its influence on selected mechanical properties of chick bone and tendon.

Day-old White Leghorn cockerels were fed skim-milk-based diets containing 0, 2, 4, 8, or 16 ppm added copper as CuSO4 for 21 days. Lysyl oxidase was extracted from bone and tendon. The recovery of activity from the extracts was linearly correlated with dietary copper (r greater than 0.90). Tests of the mechanical properties of tendon and bone indicated that tendon viscoelasticity (as measured by stress--relaxation) may not be significantly influenced by copper, whereas the ultimate torsional strength of bone is markedly decreased when the dietary copper level is below 1 ppm. Furthermore the torsional fracture characteristics of bone from copper-deficient birds demonstrated a lack of plastic deformation prior to failure that was normally seen in bone from control birds. The change in the mechanical properties of bone from copper-deficient birds appeared to be related to a decrease in the amounts of dihydroxylysinonorleucine and other lysine-derived cross-linking amino acids in bone collagen. The data indicate that the requirement for optimal growth of chicks fed skim-milk-based diets is 6--8 ppm copper, however, the requirement for normal cross-link formation in bone is less than 2 ppm copper.

Amino Acid Oxidoreductases↗
PubMed1982

Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases.

An immunocytochemical method for fixed and paraffin-embedded human breast biopsies is reported for the detection of myoepithelial and epithelial cells using antibodies to myosin and keratin, respectively, and of basement membranes using antibodies to laminin and type IV collagen. Using these markers, myoepithelial cells can be clearly distinguished in the normal breast and in the benign breast diseases sclerosing adenosis, epitheliosis, and fibroadenoma. In sclerosing adenosis, myoepithelial cells form a major cellular component. A stromally derived spindle cell is identified which stains with myosin but not with keratin antibodies (myofibroblast). These cells are seen in one-fifth of the fibroadenomas. Although cells staining with myosin antibodies are seen in the infiltrating component of all 18 carcinomas examined, elongated cells staining with both myosin and keratin antibodies (myoepithelial-like) are seen in only one infiltrating carcinoma where they are interposed at the stromal-epithelial junction of the infiltrating tumor cells. In contrast to the situation in benign breast diseases, mature myoepithelial cells form a very minor component of the majority of infiltrating ductal carcinomas. Basement membrane proteins, laminin, and type IV collagen are present in normal breast, benign breast disease, and grade I infiltrating ductal carcinomas but are absent in carcinomas of grades II and III.

Basement Membrane↗
PubMed1980

The human tumour xenograft--a valid model in experimental chemotherapy?

The chemotherapeutic response of a series of patients with bronchial carcinoma has been compared with the response of their xenografts established in immune-suppressed mice. The in situ endpoint of growth delay in subcutaneous tumours was the main parameter used to assess xenograft response, but clonogenic cell survival studies were also performed to assess the extent of cell kill associated with in vivo responses. Histology, chromosome analysis and demonstration of ectopic hormone production indicated that the xenografts retained human morphology and functional behaviour. Clinical response was assessed by serial measurement of metastases. The chemotherapeutic validity of xenografts is supported by this study in which 21 separate responses in 16 patients and their respective xenografts were similar. Metastases regressed completely in 5 out of 7 patients with oat cell carcinoma. Xenografts derived from these were also highly responsive to similar chemotherapy. In contrast, minimal responses were observed in xenografts established from two chemoresistant patients. One large cell anaplastic, 3 squamous and 4 adenocarcinomas were universally chemoresistant in patients and their xenografts. It is concluded that the bronchial carcinoma xenografts broadly retained human morphology and functional behaviour, and reproduced the pattern of chemotherapeutic response of their source tumours. The present work suggests that the incorporation of human tumour xenografts into drug development programmes is justified, although their usefulness in a predictive capacity to select appropriate chemotherapy for individual patients remains limited.

Animals↗
PubMed1980

Properties of a calcitonin receptor and adenylate cyclase in BEN cells, a human cancer cell line.

A human lung cancer cell line (BEN cells) was found to have a calcitonin-responsive adenylate cyclase. Various calcitonins and synthetic analogs stimulated adenylate cyclase activity withe same relative potency as they show in lowering blood calcium in the rat. Preincubation of the cells with calcitonin, followed by washing, led to loss of subsequent adenylate cyclase response to hormone. This was a dose-dependent phenomenon. The binding of [125I]salmon calcitonin to freshly subcultured cells was studied. The ability of calcitonins and analogs to compete for binding paralleled their efficacies in stimulating adenylate cyclase. Binding was saturable, reversible, and consisted of a single class of noninteracting sites with a mean Kd of 10.75 X 10(-10) M, K of 0.93 X 10(9)/M, and mean receptor number of 2.71 X 10(4)/cell. It is not known whether the calcitonin receptor is inappropriate to the cell of origin of the tumor. The BEN cells provide a means of isolating and studying the properties of the calcitonin receptor and of evaluating the significance for the tumor of a hormone-responsive adenylate cyclase.

Adenylyl Cyclases↗
PubMed1977

Calcitonin-responsive adenylate cyclase in a calcitonin-producing human cancer cell line.

A calcitonin-responsive adenylate cyclase has been found in a cell line of a poorly differentiated bronchial carcinoma (BEN cells). The cells have previously been shown to secrete an immunoreactive form of calcitonin in culture. Salmon calcitonin (SCT), porcine calcitonin (PCT) and human calcitonin (CT-M) all stimulated adenylate cyclase activity in particulate preparations. CT-M sulphoxide had little effect. The concentrations of the calcitonins required for half the maximum activation of adenylate cyclase were 6-8, 18 and 90 nm respectively. SCT (30pm) and CT-M (60 pm) increased the intracellular concentration of cyclic AMP from 11-2+/-0-2 (s.e.) to 18-2+/-0-2 and 16-7+/-0-2 respectively over a 2-5-min period. SCT (labelled with 125I) bound to particulate preparations of Ben cells, and competition for binding occurred with unlabelled SCT and CT-M. The concentration of SCT required for half the maximum inhibition of [125I]SCT binding was 11 nm. CT-M sulphoxide inhibited only at high concentration (3 micron). The characteristics of the adenylate cyclase response to SCT did not change over the period between cell adhesion (after subculture) and confluence. However, pre-incubation of cells for 4 h with SCT (150 nm) abolished the subsequent adenylate cyclase response of particulate preparations to further hormone. The practical difficulties encountered in purifying and quantifying the large-mol.-wt. form of CT-M secreted by BEN cells has precluded direct investigation of the potential relationship between hormone secretion and the occurrence of the calcitonin receptor. This relationship is discussed in terms of its possible biological significance.

Adenylyl Cyclases↗
PubMed1977

Lung tumours and ACTH production.

ACTH levels measured by N- and C-terminal immunoassays and cytochemical bioassay, were measured in fourteen lung tumours not associated with the ectopic ACTH syndrome and in macroscopically normal lung tissue taken from the same patients at thoracotomy. Significant concentrations of immunocative (greater than 3 ng/g wet weight) and bioactive (greater than 0.2 ng/g wet weight) ACTH were found in all the carcinoid and oat cell tumours (n=9), a combined tumour (poorly differentiated adenocarcinoma with large cell carcinoid elements), and a poorly differentiated squamous cell tumour. All the carcinoid tumours contained more C- than N-terminal ACTH immunoactivity. The squamous cell tumours (n=2), anaplastic tumours (n=2) and adenocarcinoma contained insignificant ACTH levels. There was a good correlation between the ACTH levels and the presence of secretory granules in the tumours examined ultrastructually. All the macroscopically normal samples of lung tissue contained immuno and bioactive ACTH-like material, the levels of which correlated well with ACTH levels in the tumour tissue. It is suggested that all lung tumours of carcinoid or oat cell type synthesize ACTH-like materials although clinical evidence of the ectopic ACTH syndrome may be absent. The presence of ACTH-like materials in non-tumorous lung tissue in patients with lung cancer may indicate a low level of ACTH production throughout the lung or sequestration of ACTH containing granules secreted by the tumour.

Adenocarcinoma↗