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Biomedical subjects

I A Silver

Publications and source records attributed to I A Silver.

At least 55 records · Page 3Linked to original sources
PubMed1988

Three dimensional reconstruction of branched tree structures from serial sections.

A process is described for the automatic registration and reconstruction of anatomical tree structures such as capillary networks in the microstructure of tissue. The technique uses images of, or images representing, a set of closely spaced parallel slices called "serial sections". The source of the serial sections may be MRI, multi-planar X-ray, multi-planar infra-red scans, or simple histological sections. A tree structure is defined as a structure consisting of a network of nested ducts, vessels or solid cores which branch and join with another such that one structure may appear as more than one distinct area in a single section, or in a series of sections. The reconstruction of such an object poses many problems which do not occur when restructuring objects which are so shaped that they can give rise to only one area in each section.

Animals↗
PubMed1988

Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts.

Osteoclasts and activated macrophages in culture were shown to generate an acidic microenvironment specifically in the attachment zone between the cell and the base of the culture dish. Measurements using pH microelectrodes revealed that osteoclasts, when firmly attached, could achieve a pH fall of about 1 unit min-1 to a limit value of pH 3.0 or less. Activated macrophages produced a slower fall of 0.5-2 pH units h-1 and a limit value of pH 3.6-3.7 was generally detected. The method of activation was relatively unimportant, but where macrophages formed clumps the pH effect was reinforced. Osteoclasts were also examined in situ in osteoporotic bone fragments in rabbit ear chambers, using a combination H+ and Ca2+ double-barrelled electrode. The pH readings reached a lower limit of 4.7 and the calcium concentration rose to a maximum of 40 mM in the erosion sites. In vivo such acid conditions would favor the direct extracellular action of secreted lysosomal proteinases in the degradation of collagen by both cell types.

Animals↗
PubMed1988

Growth regulation of skin cells by epidermal cell-derived factors: implications for wound healing.

Epidermal cell-derived factors (EDF), present in extracts and supernatant fluids of cultured epidermal cells, were found to stimulate the proliferation of keratinocytes but to inhibit fibroblasts. In vitro, the effect of EDF on epidermal cells resulted in an increased number of rapidly proliferating colonies composed mainly of basal keratinocytes. Control cultures grown in the absence of EDF had a high proportion of terminally differentiated cells. In fibroblast cultures EDF inhibited the ability of fibroblasts to cause contraction of collagen sponges by 90%. Epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor beta, nerve growth factor, and extracts of WI-38 cells (human embryonic lung fibroblasts) did not have this inhibitory activity. Application of EDF to surgical wounds stimulated extensive migration and proliferation of keratinocytes from remnants of glands, hair follicles, and wound edges. The restoration of complete epidermal coverage of wounds treated with EDF occurred twice as rapidly as that of control wounds. In addition, regenerating dermis in the EDF-treated wounds contained 1/5th to 1/15th as many cells as wounds treated with epidermal growth factor, urogastrone, transforming growth factor, or phosphate-buffered saline. The use of EDF to enhance re-epithelization and to prevent scar formation is proposed.

Animals↗
PubMed1988

Interactions of benztropine, atropine and ketamine with veratridine-activated sodium channels: effects on membrane depolarization, K+-efflux and neurotransmitter amino acid release.

1. The effect of benztropine, atropine and ketamine on veratridine-induced efflux of K+, membrane depolarization and release of amino acid neurotransmitters was investigated in the preparation of rat brain synaptosomes. 2. All three drugs inhibited in a concentration-dependent manner the processes measured: the most effective compound was benztropine which exhibited an approximate Kd of 2 microM. The inhibition was not competitive in nature. 3. The veratridine titration curves in the presence of drugs were sigmoid with Hill coefficients of about 1.4. 4. At higher concentrations, benztropine, atropine and ketamine blocked uptake of amino acid neurotransmitters into synaptosomes. 5. It is postulated that benztropine, atropine and ketamine interfere with the veratridine-activated influx of sodium into synaptosomes through voltage-dependent channels by acting at the same site as local anaesthetics. Interactions at this site alter allosterically binding and action of veratridine. In addition, at higher concentrations the drugs interact with the carrier proteins for amino acid neurotransmitters and block their transport.

Amino Acids↗
PubMed1988

Influence of an epidermal cell extract on skin healing and scar formation.

We have examined the possible regulatory role of epidermal cell extract(s) (ECE) on skin cells, namely fibroblasts and keratinocytes, both in vivo and in vitro with particular reference to modification of scar formation. In an experimental wound model in pigs, it was found that extracts of cultured human and pig keratinocytes stimulated replication of epidermal cells and their migration from wound edges and remnants of hair follicles and sebaceous glands, together with hair growth, but at the same time suppressed fibroblast proliferation in the dermis. Sections of healing skin wounds that had been treated with ECE showed the presence of a thick layer of epidermal cells lying on relatively sparse dermis. There was little or no contraction in treated wounds and scarring was minimal. Clinical studies of granulomatous lesions of horses and ulcerated wounds in dogs that had been treated with ECE supported these findings. In contrast to its apparently general stimulation of keratinocytes in vivo, ECE had a highly selective effect in vitro on epidermal cells plated at low density in the absence of a feeder layer, which suggests that its action in vivo may be confined to a specific sub-population of rapidly proliferating keratinocytes or alternatively mediated through a second messenger from another type of cell. The inhibitory effect of epidermal cell extract on fibroblasts in vitro was shown by its ability to prevent the contraction of collagen sponges by fibroblasts. These results suggest an important role for epidermal factors in the growth regulation of both epidermal and dermal cells during wound healing.

Animals↗
PubMed1987

Microelectrodes in medicine.

The chief applications of microelectrodes in medicine are in experimental studies of tissue and cell behaviour and of metabolism. Microprobes have been developed for a wide range of specific substrates and for the detection of bioelectric potentials. They have provided information that now forms the basis of much of our understanding of biological phenomena. Their inherent characteristics, such as fragility and 'drift', render them unsuitable for general clinical application except at the surface of organs. The heterogeneity of tissues makes it necessary to specify the exact anatomical location of microelectrode measurements and the probes themselves must be of a form that neither distorts, damages, nor stimulates reactions from, the cells or blood vessels with which they are in contact.

Animals↗
PubMed1987

Oxygen boundary crossing probabilities.

The probability that an oxygen particle will reach a time dependent boundary is required in oxygen transport studies involving solution methods based on probability considerations. A Volterra integral equation is presented, the solution of which gives directly the boundary crossing probability density function. The boundary crossing probability is the probability that the oxygen particle will reach a boundary within a specified time interval. When the motion of the oxygen particle may be described as strongly Markovian, then the Volterra integral equation can be rewritten as a generalized Abel equation, the solution of which has been widely studied.

Biological Transport, Active↗
PubMed1987

Energy relationships between ATP synthesis and K+ gradients in cultured glial-derived cell line.

In C6 astrocytoma cells respiring with glucose, 40% of the total production of ATP was provided by glycolysis. Anaerobiosis in the presence of glucose, reduced ATP synthesis by approximately 50%, increased lactate production by 30% and caused a 3-fold decline in [creatine phosphate]/[creatine] and consequently [ATP]free[ADP]free. There was no change in [K+]i which suggests that glycolytic production of ATP provides sufficient energy to ensure normal operation of the Na+/K+ pump. In the absence of glucose, [creatine phosphate]/[creatine] declined to less than 0.1 in 15 min and there was a loss of K+ from cells. A comparison of delta GATP and delta GNa,K under aerobic conditions with and without glucose, showed the former to be larger by 1 - 2 kcal. However, under O2-limited, glucose-restricted conditions delta GATP fell below the level necessary to maintain operation of the Na+/K+ pump and led to a collapse in ionic gradients.

Adenosine Triphosphate↗
PubMed1986

The role of glial cells in regulation of neurotransmitter amino acids in the external environment. I. Transmembrane electrical and ion gradients and energy parameters in cultured glial-derived cell lines.

Studies of energy parameters and intracellular ion concentrations were carried out on two glial cell lines, one derived from an astrocytoma (C6) and the other from an oligodendroglioma (TR33B), to elucidate the mechanism of transport of amino acid neurotransmitters by glial cells. Respiratory rate was 2.7-2.9 nmol/min/mg dry wt.; cytochrome c at 0.035-0.041 nmol/mg dry wt., was 23-29% reduced with a calculated turnover number 4.7-5.1 e-/s at 23 degrees C. ATP levels were high, 5.0-6.5 mM and [CrP]/[Cr] was almost 2. Membrane potentials at [K+]e = 5 mM were approximately -90 mV for C6 cells and -72 mV for TR33B. [K+]i was measured as approximately 100 mM for TR33B and 150 mM for C6 which indicated that the K+ diffusion potential was the major source of the membrane potential. [Na+]i was 5.8 mM for C6 and 20 mM for TR33B cells while free calcium was about 100 nM in both. Near Nernstian relationships were found in both types of cell between [K+]e and membrane potential over a range of 3.5-75 mM for TR33B and 5-110 mM for C6 cells. It is concluded that C6 and TR33B cell lines may be useful models for in vitro studies of some aspects of glial behavior.

Amino Acids↗
PubMed1986

The role of glial cells in regulation of neurotransmitter amino acids in the external environment. II. Mechanism of aspartate transport.

Active, high-affinity (Km = 4.4 microM) D-aspartate transport in C6 astrocytoma cells has been investigated. Uptake of radioactive D-aspartate was competitively inhibited by L-aspartate (Ki = 8.5 microM) and L-glutamate (Ki = 0.95 mM) and was essentially independent of pH between 6.2 and 7.8. The rate of uptake of labeled D-aspartate and its maximum accumulation ratio, [Asp]i/[Asp]e increased as the second power of the transmembrane electrical potential (measured by the potassium concentration gradient, [K+]i/[K+]e) which indicates that aspartate is transported with a net charge of +2. Aspartate transport rate and gradient also increased as the second power of the sodium concentration gradient, [Na+]e/[Na+]i, indicating that two Na+ are transported inward with each aspartate. The maximum gradient measured from total intra- and extracellular concentrations of aspartate showed the same dependence on electrical potential and sodium concentration gradient as that determined from the distribution of [3H]D-aspartate. This indicates that energy for aspartate uptake is provided by a combination of transmembrane electrical potential and sodium concentration gradient. At physiological [Na+]e (140 mM) and [K+]e (3.5-5 mM) the energy available for aspartate uptake substantially exceeded the maximum aspartate gradient. It is suggested that aspartate uptake by C6 cells is kinetically prevented from attaining high concentration differences and that the excess of driving forces over accumulation ratio ensures that glial high-affinity transport systems for amino acid neurotransmitters function in vivo predominantly in the direction of net uptake.

Animals↗
PubMed1986

Experimental treatment of tendon injury with heparin.

The effect of heparin on the progress of healing in the injured tendon was examined after a standard injury had been created in the Achilles tendons of New Zealand White rabbits. Half of the rabbits were then treated by the intratendinous injection of heparin. The diameters of the injured right hind and the uninjured left hind Achilles tendon and overlying skin were measured using vernier calipers before injury and at one month after injury. At this time histological analysis was carried out on all Achilles tendons and tendon dry weight, collagen concentration and DNA concentration were measured. Orientation of collagen fibres was more pronounced in treated than untreated tendons while cellularity and blood vessel density were less pronounced. Analysis by Students t-test demonstrated a statistically significant difference between treated and untreated tendons in terms of leg diameter (p less than 0.005), dry weight (p less than 0.01) and DNA concentration (p less than 0.01).

Achilles Tendon↗
PubMed1986

Changes in brain surface oxygen tension during profound hypotension induced with sodium nitroprusside or adenosine in the sheep.

Brain surface oxygen tensions were measured, in sheep (n = 8), with a seven-barrelled mini-electrode polarized by sweep potentials. Mean arterial pressure was reduced to 30 mm Hg with either sodium nitroprusside or adenosine. At this value of mean arterial pressure, oxygen supply to cerebral tissue was impaired. There was no significant difference between the two agents in the degree to which the oxygen supply was reduced.

Adenosine↗
PubMed1985

Cell interactions in post-traumatic fibrosis.

Models of reparative fibrosis, or wound healing, disclose a basic spatial relationship between inflammatory cells, fibroblasts, dividing fibroblasts and angiogenic endothelial cells. Many components of the extracellular fluid, especially steep gradients of PO2, PCO2, pH, glucose and lactate, have been measured. After components of coagulation play out their role in the first few days after injury, macrophages sense excitatory substances and signs of respiratory distress, and secrete chemoattractants for endothelial cells and fibroblasts. If excitatory substances (such as silica) are eliminated, active fibrosis ends with the restoration of the energy supply. Some of the mitogens and chemoattractants acting as intercellular messengers between these cells have been isolated and identified.

Animals↗
PubMed1985

Hypovolaemia and healing in colonic anastomoses.

Colonic anastomotic leakage is more common following emergency resections than after elective operations. Transient hypovolaemia, which is more likely to occur during emergency surgery, has been shown to impair collagen metabolism in abdominal and skin wounds but its effect on colonic anastomotic healing has not been previously examined. Acute intra-operative loss of 10 per cent circulating blood volume in rats significantly impaired collagen concentration in both ileocolic (P less than 0.02) and colocolic (P less than 0.05) anastomoses measured on the third postoperative day. This degree of blood loss did not significantly affect early anastomotic strength. Hypovolaemia leads to tissue hypoxia, and this in turn may lead to impaired anastomotic healing. Measurement of tissue oxygen tension may predict poor healing by identifying inadequate intestinal perfusion. Colonic pTO2 measured in rabbits was significantly lower than in small bowel (37 +/- 18 mmHg versus 42 +/- 18 mmHg; P less than 0.001), and fell significantly in colon following 10 per cent blood loss (P less than 0.001). We conclude that adequate intra-operative fluid replacement during colonic resection and anastomosis is a prerequisite for successful healing.

Animals↗
PubMed1985

Some effects of ischaemia and hyperglycaemia on neurotransmitter metabolism in rat brain.

30 min of low flow cerebral ischaemia (0.12 ml/min) was imposed on normal and hyperglycaemic rats. Some were allowed to recover for up to 10 h. Whole tissue homogenates, or synaptosomes from the brains of each group were examined for content of noradrenaline, dopamine and 5-HT of defined anatomical regions. In normoglycaemic rats immediately after ischaemia there was a significant reduction in the content of all three neurotransmitters in cortex, striatum and hippocampus but not in diencephalon (except possibly 5H-T) or brain stem. The amounts of all three neurotransmitters returned to control values after about 30 min reperfusion and remained so for 10 h. By contrast, no changes in neurotransmitter levels were found either during or after ischaemia in hyperglycaemic rats. Dopamine synthesis rates in the striatum were increased after ischaemia and returned to control levels in 2-3 h in normoglycaemic rats but were unaltered in hyperglycaemic animals. Binding sites for spiroperidol and LSD were compared in cortical synaptosomes and whole cortex homogenates in the presence and absence of agonists and antagonists. Both types of membrane showed similar binding properties and there was no significant change in number or character of binding sites immediately following ischaemia or during 10 h of brain reperfusion. The significance of these findings is discussed in relation to ischaemic brain damage.

Animals↗