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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 235 records · Page 13Linked to original sources

Steroid receptors in rat uteri: postmortem retention of specific binding functions in crude tissue preparations.

Steroid receptor measurement by steroid binding analysis is a clinically useful procedure. The determination of steroid binding by specific receptors is thought to reflect the biological status of the test specimen and thereby aid prediction of patient response to endocrine therapy. The need for rapid excision of a specimen and transfer to a cold environment is believed necessary to allow reliable receptor evaluation. The optimal method of processing specimens for receptor assays, however, remains to be determined. This article reports our results on the hormone specific binding functions of rat uterine estrogen and progesterone receptors in relation to their time postmortem in situ. Steroid binding by inactive (cytoplasmic) and activated (nuclear) receptors and the processes of receptor transformation, translocation and nuclear association have been studied. Contrary to generally held notions, our results indicate that the binding functions were not altered up to 1.5 hours postmortem in situ relative to their behavior in incubation media at 2 degrees C. Thus, this apparent stability of the steroid receptors, in situ, allows greater freedom in the procurement of tissues for receptor analyses in clinical and basic research studies.

Animals↗

Ultrastructural morphology of granule release from juxtaglomerular myoepithelioid and peripolar cells.

The morphology of granule release from juxtaglomerular myoepithelioid and peripolar cells has been examined. Renin release occurs from myoepithelioid granules by an unusual form of exocytosis via deep channel-like invaginations of the plasma membrane. Such release occurs towards the juxtaglomerular interstitium as well as towards the arteriolar lumen. Peripolar cell granule exocytosis occurs directly into the urinary space in sodium-depleted sheep, tentatively supporting the speculation that it may be the source of an intrarenal sodium-retaining hormone.

Animals↗

The inhibitory effect of serum from diethyldithiocarbamate treated rats on bovine adrenal dopamine-beta-hydroxylase activity.

The activity of serum dopamine-beta-hydroxylase does not depend solely on the presence of exogenous inhibitors: its activity also depends on the rate of release into plasma and is influenced by sympathetic activity or pathological conditions. This fluctuation may disguise the effect of an exogenous inhibitor on the enzyme. It has been shown in the present work that boiling of serum obtained from sodium diethyldithiocarbamate treated rats did not eliminate the dopamine-beta-hydroxylase inhibitory effect on a bovine adrenal dopamine-beta-hydroxylase preparation. Thus it is possible to measure the dopamine-beta-hydroxylase inhibitory effect of an exogenous inhibitor of this type without interference from the enzyme present in serum. Serum taken from rats treated with sodium diethyldithiocarbamate depressed in a time and dose dependent way the activity of bovine adrenal dopamine-beta-hydroxylase preparation.

Adrenal Glands↗

Fluorescence intensity profile of human lens sections.

The fluorescence intensity profiles of thin cross-sections of human lenses were determined as a function of age by scanning microspectrofluorimetry with blue light excitation close to that available in conventional slit-lamp examination (filter transmission maximum 410 nm). The fluorescence intensity of the entire nuclear region increased with age. The profile of the adult lens was manifested as a plateau, with a depressed inner region. The anterior slope (representing cortex) was nearly always more gradual than the more precipitous posterior slope. The peak fluorescence intensity was usually located at the posterior juxtacortical region. An additional shoulder occasionally appeared in the anterior juxtacortical nucleus. The fluorescence maximum for all ages occurred at 530 nm.

Adult↗

Deuterium nuclear magnetic resonance investigation of dimyristoyllecithin--dipalmitoyllecithin and dimyristoyllecithin--cholesterol mixtures.

Deuterium nuclear magnetic resonance (NMR) spectra of 1,2-dimyristoyl-3-sn-phosphatidylcholines (DMPCs) specifically deuterated in the 2-chain at one of positions 2', 3', 6', or 14' have been obtained by the quadrupole-echo Fourier transform method at 34.1 MHz (corresponding to a magnetic field strength of 5.2 T) or the pure material as a function of temperature, and in the presence of either 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC) or cholesterol as a function of temperature and composition. The results with pure DMPC and DMPC--DPPC mixtures indicate that a sharp, intense deuterium resonance is characteristic of fluid-phase lipids, whereas a broad resonance is characteristic of solid-phase lipids. There is shown to be good agreement between the deuterium NMR derived DMPC--DPPC phase diagram and that derived by using other techniques. The deuterium NMR results obtained with the DMPC--cholesterol system are not interpreted in terms of a phase diagram. They do indicate, however, that the transition breadth is increased considerably and the temperature at which the lipid chains "solidify" is depressed by the addition of cholesterol to the DMPC bilayer. The particular nature of the increase and the depression is found to be dependent on where the label is located on the lipid.

Cholesterol↗

Stereocilia mediate transduction in vertebrate hair cells (auditory system/cilium/vestibular system).

The vertebrate hair cell is a sensory receptor that responds to mechanical stimulation of its hair bundle, which usually consists of numerous large microvilli (stereocilia) and a single true cilium (the kinocilium). We have examined the roles of these two components of the hair bundle by recording intracellularly from bullfrog saccular hair cells. Detachment of the kinocilium from the hair bundle and deflection of this cilium produces no receptor potentials. Mechanical stimulation of stereocilia, however, elicits responses of normal amplitude and sensitivity. Scanning electron microscopy confirms the assessments of ciliary position made during physiological recording. Stereocilia mediate the transduction process of the vertebrate hair cell, while the kinocilium may serve primarily as a linkage conveying mechanical displacements to the stereocilia.

Animals↗

Bovine lymphocytes: erythrocyte rosettes in normal, lymphomatous and corticosteroid-treated cattle.

Spontaneous erythrocyte rosettes, antibody-complement rosettes and nonrosetting cells were enumerated for peripheral blood lymphocytes of normal adult, lymphomatous adult and immature cattle as well as for peripheral blood lymphocytes of adult cows both before and after injection of corticosteroids. Calf thymic lymphocytes were also examined for rosette formation. Results indicate significant reduction in peripheral blood lymphocyte-erythrocyte rosettes and nonrosetting cells in tumour-bearing cows with a simultaneous elevation in percent antibody-complement rosettes. Calf thymus had a significantly greater percent erythrocyte rosettes than did peripheral blood lymphocytes from the same individuals. Corticosteroid injection reduced peripheral blood lymphocytes without altering proportion of cells as erythrocyte rosettes, antibody-complement rosettes or nonrosetting cells.

Adrenal Cortex Hormones↗

Spectroscopic studies of specifically deuterium labeled membrane systems. Nuclear magnetic resonance investigation of the effects of cholesterol in model systems.

Deuterium nuclear magnetic resonance spectra of dimyristoylphosphatidylcholines specifically labeled in positions 2', 3', 4', 6', 8', 10', 12', and 14', of the 2 chain, of an N-deuteriomethylphosphatidylcholine, and of cholesterol-3alpha-d1, have been obtained by the Fourier transform method at 5.46 and 3.52 T on two "home-built" widebore superconducting magnet spectrometers, as a function of temperature and composition. Data on the specifically deuterium-labeled cholesterol molecule (in nonsonicated membrane systems) permits an estimate of the most probable angle of tilt of the sterol in the membrane, and evaluation of the order parameter (Salpha) describing rigid body motions in the bilayer. Segmental order parameters derived from the data presented allow calculation of individual chain segment projections onto the director axis and, consequently, estimation of effective chain length. It is shown that mathematical models which include chain tilt as well as those which neglect this type of rigid body motion give essentially identical results when applied to the dimyristoylphosphatidylcholine and dimyristoylphosphatidylcholine-cholesterol bilayer systems (in excess water, between 23 and 60 degrees C). Results of calculations of chain length and membrane thickness of a dimyristoylphosphatidylcholine-30 mol % cholesterol membrane system at 23 degrees C give excellent agreement when compared with recent high-resolution neutron diffraction data obtained on specifically deuterium labeled lecithin-cholesterol systems. No evidence for formation of lecithin-cholesterol complexes having lifetimes of approximately 30 ms has been found. Below the pure-lipid gel-liquid crystal phase transition temperature Tc but in the presence of cholesterol, we have obtained further evidence for 1-chain/2-chain nonequivalence. At 10 degrees C, the 2' segment of the 2 chain, but not the 2' segment of the 1 chain or the 3', 6', or 12' segments of the 2 chain, is broadened almost beyond detection. These results are in agreement with similar effects reported recently for the dipalmitoylphosphatidylcholine-cholesterol system and may indicate a bent configuration for the 2 chain, in the lecithin-cholesterol system. Further cooling below Tc results in loss of the 1-chain 2'-position signal intensity plus 2-chain 3', 6', and 12' signals simultaneously. The increase in length of the 2 chain of dimyristoylphosphatidylcholine upon addition of 30 mol % cholesterol of 23 degrees C is about 2.3 A. Addition of cholesterol to a choline-labeled lecithin results in complex behavior of the head group deuterium quadrupole splitting as a function of temperature, and cholesterol mole fraction. Above approximately 20 mol % cholesterol, the main effect is a decrease in quadrupole splitting as cholesterol content increases, the opposite effect to that observed with hydrocarbon chains.

Cholesterol↗

Light and electron microscope studies of the rat digestive tract following prolonged and short-term ingestion of chrysotile asbestos.

Rats were fed diets containing 0.5 mg or 50 mg of chrysotile asbestos each day for 1 week or 14 months and tissues of the gastrointestinal tract were examined by light and electron microscopy. At the light microscope level the oesophagus, stomach and caecum in treated animals appeared unaffected, whereas accumulation of cellular debris and Alcian blue-positive material was apparent in the ileal, rectal and colonic lumens. Electron microscope examination of the colon and ileum of rats ingesting 50 mg chrysotile/day for 14 months confirmed these findings and indicated changes in the mucosal lining cells of the ileum which were consistent with a mineral-induced cytotoxicity. These results are compared with those reported in a similar previous biochemical study and the specificity of asbestos action on certain regions of the gastrointestinal tract is discussed.

Animals↗

Nucleic acid metabolism in the rat following short-term and prolonged ingestion of chrysotile asbestos or cigarette-smoke condensate.

Rats which have ingested a natural diet containing chrysotile asbestos (50 mg/day) both in the short (one week) and long term (5-15 months) show a statistically significant increase in the incorporation of [3H]-thymidine into DNA in the small intestine mucosa, colon and rectum, stomach and spleen and a significant decrease in the incorporation of this radiolabel into liver DNA. However, short-term ingestion of similar quantities of chrysotile produced no significant change in the incorporation of [3H]-uridine into RNA in any tissues, although prolonged ingestion of the mineral induced alterations in RNA metabolism in the lung and liver. By contrast, animals ingesting a natural diet containing cigarette-smoke condensate show a significantly high incorporation of [3H]-uridine into RNA in the mucosa, submucosa, spleen and heart following short-term exposure. Long-term ingestion of this diet produces similar changes in the submucosa, spleen and lung. The apparent specificity and the mechanism whereby ingested chrysotile interferes with DNA metabolism in some body tissues is discussed.

Animals↗