Biomedical subjects

J Finch

Publications and source records attributed to J Finch.

At least 55 records · Page 3Linked to original sources

PubMed1991

Extrarenal production of calcitriol in normal and uremic humans.

We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3. The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3. In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism. Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects. These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed1991

Obligations of kinship in contemporary Britain: is there normative agreement?

This article explores the extent to which there is normative agreement in contemporary Britain about the 'proper thing to do' for relatives. Using quantitative survey data generated using the 'vignette technique', the authors assess how far certain policy and sociological assumptions about appropriate kinship obligations hold up to empirical scrutiny. They argue that there is not a straightforward consensus about a set of normative principles but that it is possible to identify patterns of normative agreement. These vary more in line with the circumstances specified in the vignettes than with the social characteristics of the respondents. There is more evidence of a consensus over procedures - that is what factors people should take into account in working out the proper thing to do for relatives - than over the substance of what should be done. The authors conclude that people do not carry around with them stable sets of values and meanings about obligations to kin, but construct them when they have to out of various materials available.

England↗

PubMed1990

Transient alterations in the expression of protease and extracellular matrix genes during metastatic lung colonization by H-ras-transformed 10T1/2 fibroblasts.

It has been proposed that tumor progression is a selective process and that only a minority of tumor cells survive this selection because they possess the phenotypic traits necessary for metastasis and organ colonization. Both proteases and extracellular matrix proteins have been implicated in invasion and metastasis formation. To examine the nature of the selection process, we transformed 10T1/2 fibroblasts with T24 H-ras and the neoR gene and selected a clonal line expressing the mutant ras gene. After i.v. injection of this line into syngeneic C3H/HeN mice, tumor cells were recovered from lungs by enzymatic treatment and selective outgrowth in G418. Less than one of 10(3) cells survived in the lung 30 min after inoculation, and these exhibited a unique phenotype. This was characterized by a propensity to lodge in the lung on reinjection; markedly enhanced mRNA levels of procollagen alpha 2(I), procollagen alpha 1(III), and fibronectin; and decreased levels of laminin, major excreted protein (procathepsin L), transin, and H-ras. Between 1 and 9 days after tumor injection, the phenotype of the cells surviving in the lung changed dramatically and exhibited a pattern of gene expression with increased protease and low matrix protein mRNA levels. This coincided with a 26-fold increase in the ability to colonize lungs on i.v. injection. Both the phenotype characterized by its propensity to arrest in the lung and that showing enhanced metastatic ability were unstable on prolonged in vitro culture. We hypothesize that two selection events have occurred. The first is for lung arrest and implantation of variants of the injected tumor with high matrix protein and low protease levels. A second selection then occurs for tumor cells that carry a favorable phenotype for invasion and proliferation which is associated with low matrix protein and high protease gene expression. These two phenotypes are represented within a clonal population of recently transformed tumor cells.

Animals↗

PubMed1990

A comparison of two methods of in vivo dosimetry for a high energy neutron beam.

Two methods of in vivo dosimetry have been compared in a high energy neutron beam. These were activation dosimetry and thermoluminescence dosimetry (TLD). Their suitability was determined by comparison with estimates of total dose, obtained using a tissue equivalent ionization chamber. Measurements were made on the central axis and a profile of a 10 x 10 cm square field and also behind a shielding block in order to simulate conditions of clinical use. The TLD system was found to provide the best estimate of total dose.

Fast Neutrons↗

PubMed1990

Extrarenal production of calcitriol.

Under normal circumstances extrarenal sources of calcitriol probably constitutes a microendocrine system involved in cell differentiation and local intercellular communication with no influence on systemic calcium homeostasis. Under pathological conditions such as chronic renal failure, extrarenal sources have the potential to normalize serum calcitriol after adequate stimulation (such as, 25(OH)D administration). Extrarenal 1,25-(OH)2D3 synthesis is controlled by physiological levels of calcitriol. However, in sarcoidosis and other granulomatous diseases, 1,25-(OH)2D3 production by macrophages is deregulated, causing severe alterations in systemic calcium homeostasis.

Animals↗

PubMed1989