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Biomedical subjects

H Cox

Publications and source records attributed to H Cox.

At least 55 records · Page 3Linked to original sources
PubMed1991

Is adrenaline released by sympathetic nerves in man?

Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline into plasma in man. This was done as a partial test of a theory of essential hypertension pathogenesis which envisages an important cotransmitter function for neuronally released adrenaline. In healthy resting men no release of adrenaline could be detected from the heart, lungs or liver. Adrenaline was released into the right renal vein but an adrenal medullary source is suspected. With the relatively limited activation of the cardiac sympathetic outflow which accompanied mental challenge and isometric exercise, cardiac adrenaline release remained undetectable. During supine bicycle exercise, which increased cardiac noradrenaline release 10-30 fold, to a mean value of 197 ng/min, cardiac adrenaline release averaged 2.36 ng/min. In two clinical conditions associated with persistently elevated plasma adrenaline concentrations, cardiac failure and adrenaline-secreting phaeochromocytoma, regional release of adrenaline was clearly evident. Thus, in normal man during exercise, and in patients with cardiac failure at rest, adrenaline is released from non-adrenal sources, and probably from sympathetic nerves. Whether neuronal adrenaline release of the degree found would be sufficient to facilitate noradrenaline release, augment sympathetically-mediated cardiovascular responses and contribute to the development of arterial hypertension remains to be tested.

Adrenal Gland Neoplasms↗
PubMed1991

Adrenaline release by the human heart.

1. Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline to plasma in humans. 2. No release of adrenaline could be detected from the heart, lungs, liver and kidneys at rest. 3. With the relatively mild activation of the cardiac sympathetic outflow associated with mental challenge and isometric exercise, cardiac adrenaline release remained undetectable. 4. During supine bicycle exercise, which increased cardiac noradrenaline release 10-20 fold, to a mean value of 128 ng/min, cardiac adrenaline release averaged 1.63 ng/min. 5. Whether neuronal adrenaline release of this degree in the heart is sufficient to facilitate noradrenaline release and to augment sympathetically mediated cardiac responses remains to be tested.

Epinephrine↗
PubMed1991

Biochemical evidence of sympathetic hyperactivity in human hypertension.

Radiotracer measures of norepinephrine overflow to plasma are well suited for studying both human sympathetic nervous system responses to mental stress and sympathetic nervous pathophysiology in human hypertension. With an experimental laboratory stressor (cognitive challenge), we noted a preferential activation of the cardiac sympathetic outflow; however, in fainting reactions ("vasovagal syncope"), which occur infrequently during the course of central venous catheter placement under local anesthesia, the converse was seen--an almost total withdrawal of cardiac sympathetic activity. In primary human hypertension (particularly in younger patients), a differentiated activation of the sympathetic outflow to the heart and kidneys is present, based on measurements of norepinephrine spillover to plasma. It is uncertain whether this is attributable to behavioral factors and represents a component of the defense reaction. We previously reported overflow of norepinephrine into the cerebrovascular circulation (with high internal jugular venous sampling) in humans. Because this is resistant to ganglion blockade, brain neurons--not the cerebrovascular sympathetics--are the presumed source. In a preliminary study, we found higher rates of norepinephrine spillover into the cerebrovascular circulation in patients with essential hypertension than in healthy subjects, suggesting that an underlying increase in central nervous system norepinephrine turnover may be the basis for the increased sympathetic outflow.

Brain↗
PubMed1990

Tissue preparation for simultaneous flow cytometric quantitation of tumour associated antigens and DNA in solid tumours.

A multiparameter flow cytometric assay for the simultaneous study of tumour associated antigens (TAA) and DNA in fresh solid tumours was devised. Cell suspensions were prepared by disaggregating unfixed solid tumour samples mechanically over a stainless steel mesh. Indirect immunofluorescence was used to identify the TAA, and DNA was stained with propidium iodide. Cell morphology was well preserved, cell clumping was negligible, and high quality indirect immunofluorescence quality indirect immunofluorescence and DNA staining were obtained. The technique is simple, rapid, and reproducible. Multiparameter assays can be developed to study prognostic indicators such as membrane oncoproteins, receptors, and multidrug resistance in solid tumours. With a suitable panel of antibodies the technique might become an aid in the differential diagnosis and biochemical diagnosis of some solid tumours.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1989

Radial ray defects and associated anomalies.

In a series of 34 patients with defects of the radial ray, 24 individuals had additional clinical manifestations. A firm syndromic diagnosis could be reached in 17 persons (TAR syndrome 4, Holt-Oram syndrome 8, Fanconi anaemia 2, VATER association 2, Radial ray-choanal atresia 1). In the remainder, no specific diagnosis could be established. The heterogeneity of radial ray syndromes has important implications for prognostication and genetic counselling.

Abnormalities, Multiple↗
PubMed1988

Polar fluorescein derivatives as improved substrate probes for flow cytoenzymological assay of cellular esterases.

Fluorescein esters are employed in assays of cell viability, membrane permeability and esterase activity. The ester most widely used, fluorescein diacetate (FDA), has the disadvantage of rapid cellular efflux of its hydrolysis product fluorescein. This is particularly problematic for flow cytoenzymology (FCE), where fluorescence is measured in individual cells allowing identification of subpopulations differing in esterase activity and/or membrane characteristics. We present a comparison of FDA with two potentially improved substrate probes for FCE, carboxyfluorescein diacetate (CFDA) and bis(carboxyethyl)-carboxyfluorescein-tetra acetoxy methyl ester (BCECF-AM). Substrates were characterized in terms of reaction and product efflux kinetics in EMT6 mouse mammary tumour cells, together with inhibition kinetics for the carbamoylating agent BCNU. Intact viable cells were analysed by FCE and spectrofluorimetry, and the latter was also used for cell sonicates and purified esterase. CFDA and BCECF-AM enter cells and are hydrolysed more slowly than FDA. CFDA and FDA hydrolyses obey Michaelis-Menten kinetics with Km values of around 19 and 2 microM, respectively, whereas BCECF-AM hydrolysis deviates from this classical behaviour. BCNU (5 X 10(-4) M) inhibits FDA and BCECF-AM hydrolyses by approximately 50%, compared to 30% for CFDA. CFDA may be partly hydrolysed by membrane-bound esterases. Efflux half-lives were 16 min, 94 min and greater than 2 h for products of FDA, CFDA and BCECF-AM, respectively. We conclude that BCECF-AM is the optimal substrate probe for FCE. This study emphasizes the need to optimize various parameters when selecting a substrate for flow cytoenzymological assay or when loading other reporter fluorochromes into cells via lipophilic esters.

Animals↗
PubMed1987

Flow cytometric quantitation of the c-myc oncoprotein in archival neoplastic biopsies of the colon.

The c-myc oncogene encoded protein product, p62c-myc, was assayed simultaneously with DNA in populations of individual nuclei extracted from archival biopsies of colonic neoplasia. Both the protein and DNA were assayed fluorimetrically using flow cytometry with a synthetic peptide induced monoclonal antibody (MYC 1-6E10) for the protein and propidium iodide for DNA. The nuclear p62c-myc levels increased progressively from normal mucosa through polyps to carcinomas. However, there was a trend for the more poorly differentiated carcinomas to exhibit lower levels than moderately and well-differentiated tumours, p = 0.085. These results agree with those published previously with the same antibody using Western blotting for protein extracted from fresh frozen tissue and immunocytochemical assessment. Furthermore, flow cytometry is able to effect discriminations between subsets in heterogeneous populations using DNA as a second parameter which Western blot bulk studies cannot.

Biopsy↗
PubMed1987

Flow cytometric quantitation of DNA and c-myc oncoprotein in archival biopsies of uterine cervix neoplasia.

The c-myc nuclear associated oncoprotein has been quantitated simultaneously with DNA in nuclei extracted from archival biopsies of uterine cervix neoplasia. The oncoprotein and DNA were measured fluorimetrically in a flow cytometer using a mouse monoclonal antibody (MYC 1-6E10) and propidium iodide. Normal biopsies exhibited higher oncoprotein levels than carcinomas (P less than 0.00001). Furthermore, the maximum fluorescence signal in the normal tissue occurred at a lower antibody concentration compared with tumour tissue. There was no correlation between oncoprotein levels and histological grade, stage of disease, age of the patients or prognosis in the carcinomas. Aneuploidy, defined as a distinct second peak separate from the diploid distribution, was not a significant feature. The c-myc oncoprotein nuclear content does not appear to be a prognostic indicator in carcinoma of the cervix from the results of these studies but there is clearly diagnostic potential, particularly for automated analysis of cervical screening.

Cervix Uteri↗
PubMed1980

The motivation and political alienation of older Americans.

Utilizing a sample of older Americans this paper focused on the relationship between their personal motivation (whether internally or externally oriented) and their feeling of political incapability, political discontentment and anomie. The individual was defined as internally oriented to the degree that he felt there was a direct causal chain between his actions and given social outcomes, and externally oriented to the degree that he thought that luck, chance or fate determined these outcomes. Following Olsen's example, political incapability was defined as a feeling that the social system is preventing one from reaching desired goals, political discontentment was defined in terms of the political world not being worth one's participation, and anomies was defined as estrangement from one's social world [1]. External orientation was found to be significantly related to feelings of political incapability, political discontentment, and anomies among older Americans. The data tended to indicate that early personal orientation toward problem solving led to generalized expectations which provide long range motivational and behavioral patterns for individuals which follow them throughout life.

Aged↗